Flashcards in Pharmacology: Katzung Intro to autonomic pharmacology Deck (45)
Where do parasympathetic preganglionic fibers originate?
In cranial nerve nuclei III, VII, IX, and X.
Where to preganglionic sympathetic fibers originate from?
T1-L5 spinal nerves.
What nerve fibers are cholinergic?
All preganglionic fibers, All parasympathetic fibers and most somatic fibers.
What are the four aspects of neurotransmitter function?
(1) Synthesis and storage
(3) Termination of action
How is acetylcholine synthesized?
Acetylcholine is synthesized by acetyl-CoA (produced in the mitochondria) and choline (transported via choline acetyl transferase)
What is the rate limiting step of ACh synthesis?
The transport of choline via acetyltransferase
What drug inhibits choline transport?
What is vesamicol?
vesamicol is a research drug that blocks the transport of ACh into vesicles by the transporter VAT.
How are ACh laden vesicles released?
Calcium influx stimulates vSNARES (VAMPs) to associate with tSNARES (SNAPs). This interaction causes the vesicles to fuse with the terminal cell membrane and release the neurotransmitters into the synaptic cleft.
What major toxin can block the fusion of vesicles with the cell membrane?
How is ACh action terminated?
Acetylcholinesterase in the synaptic cleft cleaves acetylcholine into acetate and Choline. Choline may then be reabsorbed by the cell.
Why aren't many drugs targeted at acetylcholine release/production?
Because too many different kinds of nerves use acetylcholine. The action would not be specific enough and there would be adverse effects.
What is the primary adrenergic neurotransmitter?
What are some secondary adrenergic neurotransmitters?
Acetylcholine in sweat glands and vasodilatory fibers in skeletal muscle. As well as Dopamine in renal blood vessels.
How is norepinephrine synthesized?
Tyrosine --> DOPA --> Dopamine --> Norepinephrine (inside vesicle
What is the rate limiting step of Norepinephrine synthesis?
Tyrosine --> DOPA (by tyrosine hydroxylase)
What inhibits tyrosine hydroxylase?
What is the action of monoamine oxidase (MAO) in the nerve ending?
MAO on mitochondria inactivates a portion of the Dopamine and the norepinephrine. MAO inhibitors will increase the stores of transmitters in the nerve terminals.
What is the mechanism of reserpine?
Reserpine inhibits that transport of norepinephrine into vesicles. This depletes the neurotransmitter stores.
How is norepinephrine released from adrenergic nerve terminals?
Calcium influx causes vSNARES to associate with tSNARES. This interaction causes the vesicles to fuse with the membrane and release the neurotransmitters.
How is the action of norepinephrine terminated?
Norepinephrine action is terminated by reuptake rather than metabolism
How is norepinephrine reabsorbed?
NET or DAT transporters move catecholamines from the cleft into the cells. Inside the cells the catecholamines may be metabolized by MAO or COMT.
What drug can block the release of catecholamine filled vesicles?
What are cotransmitters?
Neurotransmitters other than the acetylcholine and norepinephrine that may be released from nerve endings. They typically function in modulation of synaptic interactions.
Where are muscarinic receptors found?
(2) vascular endothelium
(3) Smooth muscle
(4) Presynaptic nerve terminals
(5) Exocrine glands
Where are nicotinic receptors located?
Nicotinic receptors are located on ion channels in ganglia and skeletal muscle end plates.
Where are alpha adrenergic receptors found?
(1) vascular smooth muscle
(2) Presynaptic nerve terminals
(3) blood platelets
Where are beta adrenergic receptors found?
(1) Most smooth muscle
(2) Cardiac muscle
(3) some presynaptic nerve terminals
What is the specific location, mechanism and function of M1 (muscarinic) receptors?
M1 receptors are found in Nerve endings. They are Gq coupled which increases IP3 and starts a DAG cascade.