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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?
ACh
What are the 3 NT used in the second synapse of the sympthatic NS?
1. ACh - sweat glands

2. NE - cardiac, smooth muscle

3. Dopamine - renal vascular smooth muscle
What are the 4 primary catecholamine NT's of the sympathetic NS?
1. Norepinephrine

2. Epinephrine

3. Dopamine

4. Serotonin
What are the 3 cotransmittors of the sympathetic NS?
1. ATP

2. Galanin

3. Neuropeptide Gamma
What type of molecules are the primary NT's of the sympathetic?
Neuroamines
What are the 4 requirements for chemical neurotransmission?
1. Mechanism to synthesize the transmitter

2. Mechanism to store and release the transmitter

3. Recognition site

4. Inactivation process
What is the process of hthe synthesis of catecholamines?
Tyrosine --> Dopa --> Dopamine --> Norepinephrine --> Epinephrine
What is the rate limiting step in the production of catecholamines?
Tyrosine --> Dopa

Hydroxylation of tyrosine
How is the rate limiting step regulated?
By phosphorylation: provides acute mechanism for increasing synthesis
Where is epinephrine/norepinephrine produced?
adrenal medulla
What are the 2 cell types in the adrenal medulla?
Those with NE only (contain no PNMT)

Those with primarily E (do contain PNMT)
How does NE get converted to E
NE diffuses from granules, and is methylated by PNMT to E in the cytoplasm, which then reenters the granules
Synthesis of PMNT is regulated by what?
Glucocorticouds secreted by the adrenal cortex

(Stress increases release of cortisol from adrenal cortex and E from adrenal medulla)
How much NT is needed to have an effect?
VERY SMALL - therefor tight regulation is needed
Where at catecholamines stored in the adrenal medulla and nerve endings?
In vesicles to protect them from degredation
What do the catecholamine storage vescles contain?
1. VMAT - vesicle monoamine transporter (uptake pump)

2. Dopamine B-hyroxylase (conversion of DA - NE)

3. Cotransmitters: ATP and NPY
Exocytotic release of vesicle contents in dependent on what?
Calcium
Control of catecholamine levels is not only neg feedback on synthesis but what else?
Pre-synnaptic release
Catecholamines induce their effects via which receptor type
GPCR
What dictates whether ligand binding in GPCR will induce excitation or inhibition?
Alpha subunit
Epinephrine binds which receptor?
B1-adrenergic receptor
What is the effects of E binding to the B1-adrenergic receptor?
Increasing cAMP levels
NE binds to what?
a1 - adrenergic receptor
NE binding to a1 - adrenergic receptor produces what effects?
Increase Free Calcium
Alpha-1 (Gq) binds what and has what effects?
E/NE, increases free Ca++
Alpha-2 (Gi) binds what and has what effects?
Ne/E, decreases cAMP
Beta-1 (Gs) binds what and has what effects?
NE/E, increases cAMP
Beta-2 (Gs) binds what and has what effects?
E, increases cAMP
What are the 2 main elements of receptor refractoriness?
1. Change (w/in a tissue) in receptor density

2. Change in receptor properties
What are the 4 steps in GPCR desensitization?
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
B arrestin causes what to happen to the GPCR?
Internalization, which gives dimunition of receptor density
What are the 3 elements of the termination of the actions of catecholamines?
1. Reuptake into nerve terminals

2. Matabolic transformation / catabolism

3. Diffusion out of the junctional cleft and uptake at the extraneuronal sites
Which protein, after release, transports NE back into the cytoplasm?
NET (NE transporter)
What is needed to get complete recycling of catecholamines?
Uptake back into the neuron AND uptake into the vesicles
What are the 2 major systems for NT uptake?
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
Which enzyme inactivates both circulating and intraneuronal amines?
Monoamine oxidase (MAO)
What are the 2 isozymes of MAO?
MAO A and MAO B
What are the 3 substrates for MAO A?
1. 5-HT (serotonin)

2. NE

3. Tryptamine
What are the 2 substrates for MAO B?
1. Dopamine

2. Tryptamine
Where does NT catabolism take place?
1. In neuron

2. In peripheral target tissue
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
What is the function of a-Methyldopa?

Clinical utility?
Inhibits L-aromatic amino acid decarboxylase (L-AAD)

Treats hypertension in pregnancy
What is the function of carbidopa?
Inhibits L-AAD in the periphery (converts Dopa --> dopamine)
What is the function of disulfiram (tetraethylthiuram)?

Clinical utility?
Inhibits dopamine hyroxylase (dopamine --> NE)

Used as a deterrent to drinking
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
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
What is the function of Guanethidine?

Clinical Utility?
Inhibits release of NE

Used as a powerful anti-hypertensive
What are 2 agonists used in treatment of parkinson's disease?
1. L-DOPA

2. Bromocriptine - selective for D2 receptors
What are 2 sympathomimetic amines: Agonists?
1. Dopamine

2. Dobutamine - used in heart failure
What are the 2 main sympathomimeic amines that promote neurotransmitter release?
1. Amphetamine

2. Methamphetamine
Are amphetamines lipid soluble, are the degraded by MAO?
Lipid soluble - they can penetrate brain

Resitant to MAO - possess an a-methyl group
What is the function of cocaine?
Inhibits neuronal reuptake of NE
What is the function of imipramine?
Inhibits reuptake of both NE and 5-HT

Used as an antidepressant
Cocaine and Imipramine blocks with uptake mechanism?
Uptake-1
What is the function of selegiline?
Inhibits Catabolism via inhibition of MAO