18,19 Introduction to Cholinergic Pharmacology (ANS I-II)

Question 1

AcH: De novo synthesis (minor)

Answer 1

2 step conversion of serine to choline (serine decarboxylase, choline N-methyl transferase, S-Adenosyl methionine). Acetylation of choline (choline acetyltransferase) in cytoplasm.

Question 2

AcH recycled (major)

Answer 2

use recycled choline from synaptic cleft.

Question 3

AcH storage

Answer 3

in synaptic vesicles. Concentraction of Ach into vesicles is done using two transporters: 1) proton ATPase (pump protons inside); 2) Ach-H+ antiport. Reserve pool: replace depot pool as it is used. Depot pool: readily available vesicles for Ach release.

Question 4

AcH release

Answer 4

there is a spontaneous baseline release. Also, stimulated release via action potential. SNARE proteins (synaptobrevin and synaptotagmin) on the vesicle interact with SNAP-25 and Syntaxin in the membrane. Interatction between the two sets of proteins places the vesicle at the membrane, ready for release. Entry of Ca++ and binding to synaptotagmin causes vesicle fusion (release).

Question 5

Acetylcholinesterase

Answer 5

found in cholinergic synapses and RBCs. High affinity for acetylcholine. Pseudocholinesterase (plasma or butyrlcholinesterase): found in plasma. T1/2 range from 8-16 hours. Concentractions may directly affect succinylcholine therapy.

Question 6

AcH Metabolite fate

Answer 6

choline is taken up by special transporter into presynaptic neuron. Coenzyme A is released from the mitochondria.

Question 7

Organs w/ Muscarinic Receptors

Answer 7

on nerves in CNS, smooth muscles, heart, lungs, eyes, etc.

Question 8

Organs w/ Nicotinic Receptors

Answer 8

skeletal muscles and neuromuscular junction (Nm); autonomic ganglia, adrenal medulla, CNS (Nn).

Question 9

Compare and contrast cholinergic receptor subtypes (muscarinic and nicotinic) with emphasis on receptor subtype’s structures (Gs, Gi, Gq or ion channel) and provide (in each case) the post-receptor mechanisms.

Answer 9