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55 Cards in this Set
- Front
- Back
What is the NT for both the parasympathetic NS and the first synapse of the sympathetic NS?
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ACh
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What are the 3 NT used in the second synapse of the sympthatic NS?
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1. ACh - sweat glands
2. NE - cardiac, smooth muscle 3. Dopamine - renal vascular smooth muscle |
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What are the 4 primary catecholamine NT's of the sympathetic NS?
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1. Norepinephrine
2. Epinephrine 3. Dopamine 4. Serotonin |
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What are the 3 cotransmittors of the sympathetic NS?
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1. ATP
2. Galanin 3. Neuropeptide Gamma |
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What type of molecules are the primary NT's of the sympathetic?
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Neuroamines
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What are the 4 requirements for chemical neurotransmission?
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1. Mechanism to synthesize the transmitter
2. Mechanism to store and release the transmitter 3. Recognition site 4. Inactivation process |
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What is the process of hthe synthesis of catecholamines?
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Tyrosine --> Dopa --> Dopamine --> Norepinephrine --> Epinephrine
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What is the rate limiting step in the production of catecholamines?
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Tyrosine --> Dopa
Hydroxylation of tyrosine |
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How is the rate limiting step regulated?
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By phosphorylation: provides acute mechanism for increasing synthesis
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Where is epinephrine/norepinephrine produced?
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adrenal medulla
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What are the 2 cell types in the adrenal medulla?
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Those with NE only (contain no PNMT)
Those with primarily E (do contain PNMT) |
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How does NE get converted to E
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NE diffuses from granules, and is methylated by PNMT to E in the cytoplasm, which then reenters the granules
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Synthesis of PMNT is regulated by what?
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Glucocorticouds secreted by the adrenal cortex
(Stress increases release of cortisol from adrenal cortex and E from adrenal medulla) |
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How much NT is needed to have an effect?
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VERY SMALL - therefor tight regulation is needed
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Where at catecholamines stored in the adrenal medulla and nerve endings?
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In vesicles to protect them from degredation
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What do the catecholamine storage vescles contain?
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1. VMAT - vesicle monoamine transporter (uptake pump)
2. Dopamine B-hyroxylase (conversion of DA - NE) 3. Cotransmitters: ATP and NPY |
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Exocytotic release of vesicle contents in dependent on what?
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Calcium
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Control of catecholamine levels is not only neg feedback on synthesis but what else?
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Pre-synnaptic release
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Catecholamines induce their effects via which receptor type
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GPCR
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What dictates whether ligand binding in GPCR will induce excitation or inhibition?
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Alpha subunit
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Epinephrine binds which receptor?
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B1-adrenergic receptor
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What is the effects of E binding to the B1-adrenergic receptor?
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Increasing cAMP levels
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NE binds to what?
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a1 - adrenergic receptor
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NE binding to a1 - adrenergic receptor produces what effects?
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Increase Free Calcium
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Alpha-1 (Gq) binds what and has what effects?
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E/NE, increases free Ca++
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Alpha-2 (Gi) binds what and has what effects?
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Ne/E, decreases cAMP
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Beta-1 (Gs) binds what and has what effects?
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NE/E, increases cAMP
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Beta-2 (Gs) binds what and has what effects?
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E, increases cAMP
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What are the 2 main elements of receptor refractoriness?
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1. Change (w/in a tissue) in receptor density
2. Change in receptor properties |
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What are the 4 steps in GPCR desensitization?
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1. Phosphrylation of the serine residues in the GPCR carboxyl tail
2. Recruitment of B arrestin 3. B arrestin decreases receptor's ability to interact with G-protein subunit 4. Upon removal of GPCR kinases (GRK), activation is terminated and de-phosphorylation can occur |
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B arrestin causes what to happen to the GPCR?
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Internalization, which gives dimunition of receptor density
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What are the 3 elements of the termination of the actions of catecholamines?
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1. Reuptake into nerve terminals
2. Matabolic transformation / catabolism 3. Diffusion out of the junctional cleft and uptake at the extraneuronal sites |
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Which protein, after release, transports NE back into the cytoplasm?
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NET (NE transporter)
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What is needed to get complete recycling of catecholamines?
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Uptake back into the neuron AND uptake into the vesicles
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What are the 2 major systems for NT uptake?
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1. Uptake 1 - reuptake of NE into the nerve endings. High affinity, low capacity system.
2. Uptake 2 - extra-neuronal uptake. Low affinity, high capacity system. Important for removing circulating amines |
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Which enzyme inactivates both circulating and intraneuronal amines?
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Monoamine oxidase (MAO)
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What are the 2 isozymes of MAO?
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MAO A and MAO B
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What are the 3 substrates for MAO A?
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1. 5-HT (serotonin)
2. NE 3. Tryptamine |
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What are the 2 substrates for MAO B?
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1. Dopamine
2. Tryptamine |
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Where does NT catabolism take place?
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1. In neuron
2. In peripheral target tissue |
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What is the function of a-methyl-p-tyrpsine?
Clinical utility? |
competitive inhibitor of tyrosine hydroxylase
No known clinical utility, possibly because it is so early in the pathway |
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What is the function of a-Methyldopa?
Clinical utility? |
Inhibits L-aromatic amino acid decarboxylase (L-AAD)
Treats hypertension in pregnancy |
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What is the function of carbidopa?
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Inhibits L-AAD in the periphery (converts Dopa --> dopamine)
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What is the function of disulfiram (tetraethylthiuram)?
Clinical utility? |
Inhibits dopamine hyroxylase (dopamine --> NE)
Used as a deterrent to drinking |
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What is the function of Reserprine?
Clinical utility? |
Inhibition of vesicular transport, blocks VMAT uptake of dopamine into vesicle
Used to treat HTN and snakebite |
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What is the function of Bretylium?
Clinical utility? |
Initially causes release of NE, then inhibits release by preventing AP from reaching firing potentials
Used to treat Ventricular fibrillation |
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What is the function of Guanethidine?
Clinical Utility? |
Inhibits release of NE
Used as a powerful anti-hypertensive |
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What are 2 agonists used in treatment of parkinson's disease?
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1. L-DOPA
2. Bromocriptine - selective for D2 receptors |
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What are 2 sympathomimetic amines: Agonists?
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1. Dopamine
2. Dobutamine - used in heart failure |
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What are the 2 main sympathomimeic amines that promote neurotransmitter release?
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1. Amphetamine
2. Methamphetamine |
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Are amphetamines lipid soluble, are the degraded by MAO?
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Lipid soluble - they can penetrate brain
Resitant to MAO - possess an a-methyl group |
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What is the function of cocaine?
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Inhibits neuronal reuptake of NE
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What is the function of imipramine?
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Inhibits reuptake of both NE and 5-HT
Used as an antidepressant |
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Cocaine and Imipramine blocks with uptake mechanism?
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Uptake-1
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What is the function of selegiline?
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Inhibits Catabolism via inhibition of MAO
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