neurotrans prep
This commit is contained in:
ackman678
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## Neurotransmitters
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* Many different kinds, over 100
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* There are two main types– small molecule neurotransmitters and neuropeptides
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* Abnormalities of neurotransmitter function contributes to wide range of neurological diseases and psychiatric disorders
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* More than 100 different molecules
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* Two main types–
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* small molecule neurotransmitters
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- acetylcholine, amino acids, biogenic amines, purines
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* peptide neurotransmitters
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- polypeptides, 3–36 amino acids in length and often derived from longer polypeptides
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Note:
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So we already defined what a neurotransmitter is. It is a substance that must be present inside a presynaptic neuron, it’s release must be dependent on calcium flux from an AP, and it must have specific receptors on the postsynaptic neuron.
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We already defined what a neurotransmitter is. It is a substance that must be present inside a presynaptic neuron, it’s release must be dependent on calcium flux from an AP, and it must have specific receptors on the postsynaptic neuron.
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---
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Abnormalities of neurotransmitter function contributes to wide range of neurological diseases and psychiatric disorders
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## Major categories of neurotransmitters
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two types: very small molecule and big molecule neurotransmitters.
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* Small molecule neurotransmitters– acetylcholine, amino acids, biogenic amines, purines
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* Peptide neurotransmitters– 3-36 amino acid polypeptides, often derived from longer polypeptides
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--
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## Synaptic vesicle types
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<div><figcaption class="big">small clear-core vesicles</figcaption><img src="figs/Neuroscience5e-Fig-05.05-2R_copy_30d366b.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></div>
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<div><figcaption class="big">large dense-core vesicles</figcaption><img src="figs/Neuroscience5e-Fig-05.05-4R_copy_0b0e2ec.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></div>
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Note:
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Neurons very often make both a conventional neurotransmitter (such as glutamate, GABA or dopamine) and one or more neuropeptides. Peptides are generally packaged in large dense-core vesicles, and the co-existing neurotransmitters in small synaptic vesicles.
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The large dense-core vesicles are often found in all parts of a neuron, including the soma, dendrites, axonal swellings (varicosities) and nerve endings, whereas the small synaptic vesicles are mainly found in clusters at presynaptic locations.
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This refers to the larger amount of material inside the dense-core vesicles, which contain not only neurotransmitters, but also proteases and other peptide chains that have been cleaved from the active neurotransmitter. Greater electron scattering in EM.
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Chemical fixation
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: for biological specimens fixation aims to stabilize the specimen's macromolecular structure by chemical crosslinking of proteins with aldehydes such as formaldehyde and glutaraldehyde and lipids with osmium tetroxide.
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---
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## Examples of small-molecule neurotransmitters
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## Small-molecule neurotransmitters
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<div>
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<figure><figcaption class="big">acetylcholine</figcaption><img src="figs/Neuroscience5e-Fig-06.01-1R_copy_6024655.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 6.1</figcaption></figure>
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<figure style="margin:25px 0;"><figcaption class="big">purines</figcaption><img src="figs/Neuroscience5e-Fig-06.01-3R_copy_2d816ba.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 6.1</figcaption></figure>
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</div>
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<div><figcaption class="big">amino acids</figcaption><img src="figs/Neuroscience5e-Fig-06.01-2R_copy_55575eb.jpg" width="400px"><figcaption>Neuroscience 5e Fig. 6.1</figcaption></div>
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<div><figcaption class="big">amino acids</figcaption><img src="figs/Neuroscience5e-Fig-06.01-2R_copy_55575eb.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 6.1</figcaption></div>
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<div><figcaption class="big">biogenic amines</figcaption><img src="figs/Neuroscience5e-Fig-06.01-4R_copy_6c270be.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 6.1</figcaption></div>
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Note:
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Not expected to know chemical formulas for any neurotransmitters
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---
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## Examples of small-molecule neurotransmitters
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<figure><figcaption class="big">biogenic amines</figcaption><img src="figs/Neuroscience5e-Fig-06.01-4R_copy_6c270be.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 6.1</figcaption></figure>
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Note:
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*Most of which share a hydroxylated benzene ring*
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*Catechol, also known as pyrocatechol or 1,2-dihydroxybenzene, is an organic compound with the molecular formula C6H4(OH)2*
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---
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## Examples of peptide neurotransmitters
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## Peptide neurotransmitters
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<figure><figcaption class="big">peptides</figcaption><img src="figs/Neuroscience5e-Fig-06.01-5R_copy_3c25836.jpg" height="300px"><figcaption>methionine enkephalin: an endogenous opioid peptide; Neuroscience 5e Fig. 6.1</figcaption></figure>
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Note:
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- also called neuropeptides
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- usually 3-30 amino acids long
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- more than 100 peptides
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---
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## Neurotransmitter release can be regulated at many steps
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## Neurotransmitter synthesis
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* Synthesis–
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* Small molecules are generated from biosynthetic enzymes
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* Neuropeptides are generated by translation followed by post-translational processing
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* Packaging into vesicles– requires specific transporters on vesicle membrane, there are different types of vesicles, small clear-core (e.g. ACh and amino acids) and large dense-core (neuropeptides). Biogenic amines can be in either vesicle type. Location in synapses is different
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* Release– small clear-core vesicles release fast, large dense-core vesicles take more effort
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<div style="font-size:0.8em;">
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<div></div>
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* Synthesis can occur
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* at the soma (neuropeptides)
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* at synaptic terminals (small molecule transmitters)
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* Vesicle packaging– requires specific transporters on vesicle membrane. There are small clear-core vesicles (ACh and amino acids) and large dense-core (neuropeptides). Biogenic amines can be in either vesicle type.
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</div>
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Note:
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Small molecules are generated from biosynthetic enzymes
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Neuropeptides are generated by translation followed by post-translational processing
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<!-- *synthesis, packaging, secretion, and removal of neurotransmitters*
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<figure><img src="figs/Neuroscience5e-Fig-05.03-0R_a8b0a13.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 5.3</figcaption></figure> -->
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@@ -79,13 +98,21 @@ large dense-core vesicles
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: electron dense centers
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: 90–250 nm diameter
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<!-- Release– small clear-core vesicles release fast, large dense-core vesicles take more effort. Location in synapses is different -->
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---
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## Small molecule transmitters are synthesized at the presynaptic terminal
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<div style="width:600px;float:left;font-size:0.8em;">
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<div></div>
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Enzymes produced in nerve cell body are transported down axon. Neurotransmitter is synthesized and packaged at synaptic terminal.
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<figure><img src="figs/Neuroscience5e-Fig-05.05-1R_copy_4507f9b.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></figure>
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</div>
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<div style="float:left"><img src="figs/Neuroscience5e-Fig-05.05-1R_copy_4507f9b.jpg" height="450px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></div>
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Note:
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@@ -99,9 +126,14 @@ Note:
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## Peptide transmitters are synthesized in the cell body
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<div style="width:600px;float:left;font-size:0.8em;">
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<div></div>
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Neuropeptides are synthesized in the nerve cell body, loaded into vesicles, and transported down the axon via microtubules.
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<figure><img src="figs/Neuroscience5e-Fig-05.05-3R_copy_e9ebd70.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></figure>
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</div>
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<div style="float:left"><img src="figs/Neuroscience5e-Fig-05.05-3R_copy_e9ebd70.jpg" height="450px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></div>
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Note:
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@@ -111,26 +143,6 @@ Note:
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* proteolytic processing of propeptides by enzymes to produce peptide neurotransmitter
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* peptide neurotransmitter diffuses away, degraded by proteolytic enzymes (typically on extracellular surface)
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---
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## Synaptic vesicle types
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<div><figcaption class="big">small clear-core vesicles</figcaption><img src="figs/Neuroscience5e-Fig-05.05-2R_copy_30d366b.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></div>
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<div><figcaption class="big">large dense-core vesicles</figcaption><img src="figs/Neuroscience5e-Fig-05.05-4R_copy_0b0e2ec.jpg" width="300px"><figcaption>Neuroscience 5e Fig. 5.5</figcaption></div>
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Note:
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Neurons very often make both a conventional neurotransmitter (such as glutamate, GABA or dopamine) and one or more neuropeptides. Peptides are generally packaged in large dense-core vesicles, and the co-existing neurotransmitters in small synaptic vesicles.
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The large dense-core vesicles are often found in all parts of a neuron, including the soma, dendrites, axonal swellings (varicosities) and nerve endings, whereas the small synaptic vesicles are mainly found in clusters at presynaptic locations.
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This refers to the larger amount of material inside the dense-core vesicles, which contain not only neurotransmitters, but also proteases and other peptide chains that have been cleaved from the active neurotransmitter.
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Greater electron scattering in EM:
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Chemical fixation – for biological specimens aims to stabilize the specimen's mobile macromolecular structure by chemical crosslinking of proteins with aldehydes such as formaldehyde and glutaraldehyde, and lipids with osmium tetroxide.
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---
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## Large dense-core vesicles release after high frequency AP stimulation
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@@ -183,14 +195,20 @@ ACh: skeletal muscle excitation vs release from vagus nerve that slows down hear
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* Ligand gated channel that depolarizes skeletal muscle fibers vs g-protein coupled receptor that results in hyperpolarization of cardiomyocytes.
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--
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## Acetylcholine
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choline
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: a water soluable essential nutrient
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: quaternary ammonium salt
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: present in plant and animal tissues
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: choline is part of phophatidylcholine and sphingolipids (sphingomyelin in myelin) phospholipids on cell membranes
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: also acetylcholine precursor
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<figure><figcaption class="big">
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**choline acetyltransferase** (synthesis)
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**acetylcholinesterase** (degradation)
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</figcaption><img src="figs/Neuroscience5e-Fig-06.02-0_f4bacb8.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 6.2</figcaption></figure>
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---
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## Acetylcholine synthesis
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<figure>
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<img src="figs/Neuroscience5e-Fig-06.02-0_f4bacb8.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 6.2</figcaption></figure>
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Note:
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@@ -198,7 +216,7 @@ from krebs cycle you get Acetyl CoA. Na-Choline cotransporter exchanges Na ions
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choline acetyltransferase...
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VAChT packs ACh into vesicles
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VAChT packs ACh into vesicles using the acidic vesicle's proton gradient. The gradient is established through active transport by the standard vacuolar H+-ATPase (V-ATPase), a highly conserved enzyme to convert ATP hydrolysis energy to proton transport across membranes.
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--
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@@ -274,7 +292,7 @@ Glutamate (glutamic acid) is non-essential a.a. (meaning non-essential per dieta
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*Monosodium glutamate (MSG, also known as sodium glutamate) is the sodium salt of glutamic acid*
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--
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---
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## Glutamate
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@@ -283,9 +301,13 @@ Glutamate (glutamic acid) is non-essential a.a. (meaning non-essential per dieta
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Note:
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system A transporter 2 (SAT2) transports glutamine into presynaptic terminal. Metabolized into glutamate by mitochondrial enzyme glutaminase. Also glucose metabolism from Krebs cycle can also produce glutamate. Packaged into vesicles by vesicular glutamate transporters (VGLUT). 3 different VGLUTs identified.
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Metabolized into glutamate by mitochondrial enzyme glutaminase. Also glucose metabolism from Krebs cycle can also produce glutamate. Packaged into vesicles by vesicular glutamate transporters (VGLUT). 3 different VGLUTs identified.
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Removed from cleft by excitatory a.a. transporters (EAATs). These are family of 5 Na⁺ dependent glutamate cotransporters. Some in glial cells, some in presynaptic terminals. Glutamate in glial cells by EAAT converted into glutamine by enzyme glutamine synthetase. Then transporter out by different transporter system N transporter 1 (SN1) then back into nerve cells by SAT2.
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Removed from cleft by excitatory a.a. transporters (EAATs). These are family of 5 Na⁺ dependent glutamate cotransporters. Some in glial cells, some in presynaptic terminals.
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Glutamate in glial cells by EAAT converted into glutamine by enzyme glutamine synthetase.
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Glutamine then transported out by different transporter system N transporter 1 (SN1) then back into nerve cells by system A transporter 2 (SAT2).
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essential AA: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
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@@ -298,6 +320,13 @@ essential AA: histidine, isoleucine, leucine, lysine, methionine, phenylalanine,
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Note:
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* synthesized from **glutamine** by **glutaminase**
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* packaged into vesicles by vesicular glutamate transporters (**VGLUT**) using proton gradient setup by V-ATPase
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* removed from cleft by excitatory amino acid transporter **EAAT**
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* converted into glutamine by glutamine synthetase in the glial cell
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* tranported back to neuron via system N transporter 1 (**SN1**) and system A transporter 2 (**SAT2**)
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--
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## Glutamate synthesis video summary
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@@ -312,11 +341,11 @@ ACh role in Alzheimers: basal forebrain innervation to neocortex vs hippocampus.
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## GABA and glycine
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* Most inhibitory neurons use one or the other
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* Inhibits the ability to fire action potentials
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* GABA (gamma-aminobutyric acid) made from glutamate by glutamic acid decarboxylase (GAD), requires Vitamin B6 as cofactor. B6 deficiency can lead to loss of synaptic transmission
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* Inhibitory neurons primarily use GABA or glycine
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* Activation of GABA or glycine receptors typically reduces probability of firing action potentials
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* GABA (gamma-aminobutyric acid)– made from glutamate by glutamic acid decarboxylase (GAD)
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* GAD requires Vitamin B6 as cofactor
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* Glycine– about 1/2 of neurons in spinal cord use glycine
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* Both GABA and glycine are rapidly taken up by glia and neurons
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* Hyperglycinemia– defect in glycine uptake and removal leading to severe mental retardation
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Note:
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@@ -348,27 +377,40 @@ Strychnine
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: highly toxic, colorless, bitter crystalline alkaloid
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: from *Strychnos nux-vomica* native to India, Sri Lanka, and Indonesia
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---
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--
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## Synthesis, release, and reuptake of the inhibitory neurotransmitters GABA and glycine
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## Synthesis of the inhibitory neurotransmitter GABA
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<figure><img src="figs/Neuroscience5e-Fig-06.08-1R_ec0f42e.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 6.8</figcaption></figure>
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Note:
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transported into vesicles by vesicular inhibitory amino acid transporter (VIAAT)
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synthesized from glutamate by glutamic acid decarboxylase (**GAD**)
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Removal by neurons and glia by Na⁺ dependent cotransporters for GABA called GATs
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transported into vesicles by vesicular inhibitory amino acid transporter (**VIAAT**), using proton gradient setup by V-ATPase.
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--
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Removal by neurons and glia by Na⁺ dependent cotransporters for GABA called **GATs**
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## Synthesis, release, and reuptake of the inhibitory neurotransmitters GABA and glycine
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---
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## Synthesis the inhibitory neurotransmitters glycine
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<figure><img src="figs/Neuroscience5e-Fig-06.08-2R_4f2491c.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 6.8</figcaption></figure>
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Note:
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Synthesized from glucose by serine hydroxy-methlytransferase (**GAD**)
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Transported into vesicles by vesicular inhibitory amino acid transporter (**VIAAT**), using proton gradient setup by V-ATPase.
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Removal by neurons and glia by Na⁺ dependent glycin cotransporters **GATs**
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taurine and beta-alanine (other amino acids) can act as agonists for glycine receptors and also gaba receptors to some degree [Mori:2002]
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[Mori:2002]: Mori M., Gahwiler B. H. and Gerber U. (2002) Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro. J. Physiol. 539, 191–200
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---
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## Small molecule neurotransmitters
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@@ -396,7 +438,7 @@ Note:
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---
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## Biogenic amines
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## Monoamine neurotransmitters
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* Catecholamines– dopamine, norepinephrine, and epinephrine
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* Histamine
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@@ -406,7 +448,7 @@ Note:
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Note:
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Biogenic amines regulate many functions in the CNS and PNS. Ranging from homeostatic functions to cognition and attention.
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Monoamines (a subset of biogenic amines. Biogenic amines are monoamines + trace amines like like tryptamine, phenethylamine) regulate many functions in the CNS and PNS. Ranging from homeostatic functions to cognition and attention.
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* All come from same synthesis pathway
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* defects in function implicated in many psychiatric disorders
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@@ -434,7 +476,7 @@ Note:
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* Made by substantia nigra pars compacta (which connects to corpus striatum for coordination of body movements)
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* Does not cross the blood brain barrier, but levadopa (L-DOPA) does
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* Parkinson’s treatments include L-DOPA plus degradation enzyme inhibitors
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* Cocaine inhibits uptake of dopamine (inhibits DAT)
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* Cocaine works by inhibiting the dopamine cotransporter DAT
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Note:
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@@ -480,7 +522,7 @@ striatum.
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anterior cingulate cortex
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-->
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--
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---
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## Projections from dopaminergic neurons in the human brainstem
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@@ -506,7 +548,7 @@ Note:
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* also called noradrenaline
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* Comes from dopamine by way of dopamine-β-hydroxylase
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* Sympathetic ganglion cells use it– project to visceral motor system (fight or flight response)
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* Used as a transmitter from locus coeruleus in brainstem– projects to areas that are involved in sleep, attention, and feeding
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* Used as a transmitter from locus coeruleus in brainstem (rostral pons)– projects to areas that are involved in sleep, attention, and feeding
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* Its reuptake mechanism, the norepinephrine transporter (NET), is a target of amphetamines
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Note:
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@@ -517,7 +559,15 @@ Norep transporter (NET) is a Na⁺ depedent cotranporter. NET is a target of amp
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alpha and beta adrengergic receptors. GPCRs. Some alphas lead to slow depolarization. Some lead to slow hyperpolarization (acting on different K⁺ channels).
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--
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norepinephrine also released into blood by adrenal medulla of adrenal gland
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locus coeruleus
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: input– hypothalamus, cingulate cortex, amygdala, cerebellum, raphe nuclei
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: output– everywhere, spinal cord, brainstem, cerebellum, hypothalamus, thalamus, amygdala, cerebral cortex
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: activation mediates an excitatory effect, giving rise to arousal/wakefulness
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---
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## Projections from noradrenergic neurons in the human brainstem
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@@ -536,22 +586,21 @@ Note:
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Note:
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---
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* Epinephrine/Adrenaline– present at lower levels than the others
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* Epinephrine made by neurons in rostral medulla. Project to thalamus and hypothalamus
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<!--
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## Epinephrine
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* Adrenaline– present at lower levels than the others
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* Made by neurons in rostral medulla. Project to thalamus and hypothalamus
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Note:
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--
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## Projections from adrenergic neurons in the human brainstem
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<figure><img src="figs/Neuroscience5e-Fig-06.11-3R_9d1377d.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 6.11</figcaption></figure>
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-->
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Note:
|
||||
|
||||
---
|
||||
|
||||
@@ -560,47 +609,54 @@ Note:
|
||||
* 5-hydroxytryptamine (5-HT)
|
||||
* Made from tryptophan
|
||||
* Reuptake by specific serotonin transporters
|
||||
* Many antidepressants act by inhibiting serotonin reuptake (selective serotonin reuptake inhibitors-SSRIs). Prozac, Zoloft
|
||||
* Many antidepressants act by inhibiting serotonin reuptake (selective serotonin reuptake inhibitors-SSRIs; Prozac, Zoloft)
|
||||
* Found primarily in groups of neurons in the raphe region of the pons and upper brainstem
|
||||
* The raphe nucleus projects widespread in forebrain areas that are implicated in sleep and wakefulness and mood
|
||||
|
||||
Note:
|
||||
|
||||
VMAT loads this (as well as other monoamines) into synaptic vesicles.
|
||||
* dorsal raphe and median raphe nuclei. In brain stem. raphe nuclei just ventral to the 4th ventricle stretching from medulla
|
||||
* vesiclular monoamine transporter **VMAT** loads this (as well as other monoamines) into synaptic vesicles.
|
||||
|
||||
turkey/tryptophan—> sleep? Yes— but not really, you’d have to eat a lot more (3x more according to tryptophan supplements) than typically at thanksgiving meal.
|
||||
|
||||
[http://www.snopes.com/food/ingredient/turkey.asp](http://www.snopes.com/food/ingredient/turkey.asp)
|
||||
|
||||
Chicken and ground beef contain almost the same amount of tryptophan as turkey — about 350 milligrams per 4-ounce serving.
|
||||
Chicken and ground beef contain almost the same amount of tryptophan as turkey — about 350 milligrams per 4-ounce serving. Swiss cheese and pork actually contain more tryptophan per gram than turkey,
|
||||
|
||||
Swiss cheese and pork actually contain more tryptophan per gram than turkey,
|
||||
The amount of tryptophan in a single 4-ounce serving of turkey (350 milligrams) is also lower than the amount typically used to induce sleep. The recommendations for tryptophan supplements to help you sleep are 500 to 1,000 milligrams. For depression it can be 3000 mg or more
|
||||
|
||||
The amount of tryptophan in a single 4-ounce serving of turkey (350 milligrams) is also lower than the amount typically used to induce sleep. The recommendations for tryptophan supplements to help you sleep are 500 to 1,000 milligrams.
|
||||
|
||||
[http://www.webmd.com/food-recipes/the-truth-about-tryptophan?page=2](http://www.webmd.com/food-recipes/the-truth-about-tryptophan?page=2)
|
||||
[http://www.webmd.com/food-recipes/the-truth-about-tryptophan?page=2](http://www.webmd.com/food-recipes/the-truth-about-tryptophan?page=2):
|
||||
|
||||
>The small, all-carbohydrate snack is tryptophan's ticket across the blood-brain barrier, where it can boost serotonin levels. So have your turkey, Somer says, because it will increase your store of tryptophan in the body, but count on the carbohydrates to help give you the mood boost or the restful sleep.
|
||||
|
||||
>"Research shows that a light, 30 gram carbohydrate snack just before bed will actually help you sleep better," Somer says.
|
||||
|
||||
---
|
||||
|
||||
## Histamine
|
||||
|
||||
* Made from histidine, metabolized by monoamine oxidase
|
||||
* Made by neurons in hypothalamus that send projections to all regions of the brain and spinal cord
|
||||
* Made from histidine, a metabolite of monoamine oxidase
|
||||
* Released by neurons in hypothalamus (tuberomammilary nucleus) that send projections to all parts of the brain and spinal cord
|
||||
* Mediates arousal and attention
|
||||
* Histamine receptors are in the immune system and in the CNS. The sedative side effects of Benadryl act through the CNS
|
||||
* Histamine receptors are in the immune system and in the CNS. Sedative effects of diphenhydramine (Benadryl) act through the CNS
|
||||
|
||||
Note:
|
||||
|
||||
* synthesized from histidine by
|
||||
|
||||
* H1 receptors (antagonists used for treating motion sickness because role in vestibular function)
|
||||
* H2 receptors control secretion of gastrci acid in digestive system
|
||||
|
||||
*transported into vesicle by VMAT as catecholamines*
|
||||
|
||||
---
|
||||
|
||||
diphenhydramine
|
||||
: benadryl
|
||||
: inhibits H1 receptors
|
||||
: also has some serotonin reuptake inhibitor capability
|
||||
: also has some anticholinergic (muscarinic) capability
|
||||
|
||||
--
|
||||
|
||||
## Synthesis of histamine and serotonin
|
||||
|
||||
@@ -608,24 +664,6 @@ Note:
|
||||
|
||||
Note:
|
||||
|
||||
--
|
||||
|
||||
## Widespread projections from histaminergic and serotonergic neurons in the human brain
|
||||
|
||||
<figure><img src="figs/Neuroscience5e-Fig-06.13-0_2e4abbc.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 6.13</figcaption></figure>
|
||||
|
||||
|
||||
Note:
|
||||
|
||||
|
||||
--
|
||||
|
||||
## Serotonin synthesis video summary
|
||||
|
||||
<div><video height=400px controls src="figs/Animation06-05NeurotransmitterPathwaysSerotonin.mp4"></video><figcaption>Neuroscience 5e Animation 6.5</figcaption></div>
|
||||
|
||||
Note:
|
||||
|
||||
---
|
||||
|
||||
## Peptide neurotransmitters
|
||||
@@ -651,7 +689,7 @@ Note:
|
||||
Note:
|
||||
|
||||
|
||||
--
|
||||
---
|
||||
|
||||
## Synthesis of neuropeptides
|
||||
|
||||
@@ -687,29 +725,15 @@ ACTH
|
||||
: increases production of cortisol in adrenal glands
|
||||
|
||||
|
||||
--
|
||||
|
||||
<!--
|
||||
## Synthesis of neuropeptides
|
||||
|
||||
<figure><img src="figs/Neuroscience5e-Fig-06.16-2R_11ddd71.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 6.16</figcaption></figure>
|
||||
|
||||
|
||||
Note:
|
||||
|
||||
Proteolytic processing of the pre-propeptides, pre-proopiomelanocortin and pre-proenkaphalin
|
||||
-->
|
||||
|
||||
--
|
||||
|
||||
## Examples of peptide transmitters– Substance P
|
||||
|
||||
* Substance P– 16 amino acid peptide
|
||||
* Present in human hippocampus, neocortex, and GI tract (hence a brain-gut peptide)
|
||||
* Involved in the perception of pain
|
||||
* Released from C-fibers which carry information about pain and temperature
|
||||
|
||||
Note:
|
||||
|
||||
accidental discovery of substance P. Ominous sounding compound from Area 51? No. It was an unidentified component of powder extracts from brain and intestine. High conc. in hippocampus, neocortex, and GI tract. A brain/gut peptide. Release of Subst P in cfibers can be inhibited by spinal interneurons releasing opioid peptides.
|
||||
|
||||
---
|
||||
|
||||
@@ -730,11 +754,27 @@ Opioids are named because they bind to same postsynaptic receptors as opium.
|
||||
|
||||
Opioid peptides distributed throughout the brain. Colocalize with GABA and 5-HT. Tend to be depressants. They act like analgesics when injected intracerebrally. Initiate effects through GPCRs. Activate at low concentrations (nM to uM). mu, delta, kappa opioid receptor subtypes play role in reward and addiction. mu-receptor is primary site for opiate drugs.
|
||||
|
||||
--
|
||||
|
||||
## Examples of peptide transmitters– Substance P
|
||||
|
||||
* Substance P– 16 amino acid peptide
|
||||
* Present in human hippocampus, neocortex, and GI tract (hence a brain-gut peptide)
|
||||
* Involved in the perception of pain
|
||||
* Released from C-fibers which carry information about pain and temperature
|
||||
|
||||
Note:
|
||||
|
||||
accidental discovery of substance P. Ominous sounding compound from Area 51? No. It was an unidentified component of powder extracts from brain and intestine. High conc. in hippocampus, neocortex, and GI tract. A brain/gut peptide. Release of Subst P in cfibers can be inhibited by spinal interneurons releasing opioid peptides.
|
||||
|
||||
|
||||
|
||||
|
||||
---
|
||||
|
||||
## Unconventional neurotransmitters– Cannabinoids
|
||||
|
||||
<div style="font-size:0.8em;">
|
||||
<div style="width:600px;float:left;font-size:0.7em;">
|
||||
<div></div>
|
||||
|
||||
* Cannabinoids
|
||||
@@ -748,7 +788,7 @@ Opioid peptides distributed throughout the brain. Colocalize with GABA and 5-HT.
|
||||
|
||||
</div>
|
||||
|
||||
<div><figcaption class="big">CB1 expression in rodent</figcaption><img src="figs/Neuroscience5e-Box-06G-4R_ece2b22.jpg" height="150px"><figcaption>Neuroscience 5e Box 6</figcaption></div>
|
||||
<div style="float:left;"><figcaption class="big">CB1 expression in rodent</figcaption><img src="figs/Neuroscience5e-Box-06G-4R_ece2b22.jpg" width="300px"><figcaption>Neuroscience 5e Box 6. M. Herkenham, NIMH</figcaption></div>
|
||||
|
||||
<!-- <div><img src="figs/Neuroscience5e-Box-06G-3R_64fbca1.jpg" height="100px"><figcaption>Neuroscience 5e Box 6</figcaption></div> -->
|
||||
|
||||
@@ -759,6 +799,8 @@ Unconventional neurotransmitters. Released from neurons, regulated by Ca²⁺, a
|
||||
|
||||
These endocannabinoids are actually unsaturated fatty acids from enzymatic digestion of membrane lipids. Production stimulated by second messengers within postsynaptic neuron, typically a rise in postsynaptic Ca²⁺ concentration.
|
||||
|
||||
Ohno-Shosaku *Neuron* 2001: endocannabinoids act on cannabinoid receptors (CB1) to reduce GABA release from presynaptic inhibitory neurons. Inhibiting inhibition (disinhibition).
|
||||
|
||||
-anandamide
|
||||
-2-arachidonylglycerol (2-AG)
|
||||
|
||||
@@ -786,12 +828,9 @@ Psychotropic
|
||||
: psychoactive
|
||||
: chemical substance that changes brain function resulting in altered perception, mood, or conciousness
|
||||
|
||||
* cannabis sativa
|
||||
* cannabis indica
|
||||
* phytocannabinoids (85 active identified in cannabis)
|
||||
|
||||
* used for hemp (fiber, oil, seed)
|
||||
* A hybrid Cannabis strain (White Widow) (which contains one of the highest amounts of Cannabidiol), flower coated with trichomes, which contain more THC than any other part of the plant
|
||||
* cannabis sativa | cannabis indica
|
||||
* used for hemp (fiber, oil, seed)
|
||||
* phytocannabinoids (85 active identified in cannabis)
|
||||
|
||||
THC:
|
||||
* agonist of both CB1 and CB2
|
||||
@@ -842,7 +881,3 @@ Other cannabinoid-like compounds found in other plants (e.g. Echinacea). Some li
|
||||
## Summary
|
||||
|
||||
<figure><img src="figs/Neuroscience5e-Tab-06.01_copy_98ede88.jpg" height="400px"><figcaption>Neuroscience 5e Table 6.1</figcaption></figure>
|
||||
|
||||
Note:
|
||||
|
||||
---
|
||||
|
||||
Reference in New Issue
Block a user