Mobilization of the readily releasable pool of acetylcholine from a sympathetic ganglion by tityustoxin in the presence of vesamicol.
The present experiments tested whether preganglionic stimulation and direct depolarization of nerve terminals by tityustoxin could mobilize similar or different pools of acetylcholine (ACh) from the cat superior cervical ganglia in the presence of 2-(4-phenylpiperidino)cyclohexanol (vesamicol, AH5183), an inhibitor of ACh uptake into synaptic vesicles. In the absence of vesamicol, both nerve stimulation and tityustoxin increased ACh release. In the presence of vesamicol, the release of ACh induced by tityustoxin was inhibited, and just 16% of the initial tissue content could be released, a result similar to that obtained with electrical stimulation under the same condition. When the impulse-releasable pool of ACh had been depleted, tityustoxin still could release transmitter, amounting to some 10% of the ganglion's initial content. This pool of transmitter seemed to be preformed in the synaptic vesicles, rather than synthesized in response to stimuli, as tityustoxin could not release newly synthesized [3H]ACh formed in the presence of vesamicol, and hemicholinium-3 did not prevent the toxin-induced release. In contrast to the results with tityustoxin, preganglionic stimulation could not release transmitter when impulse-releasable or toxin-releasable compartments had been depleted. Our results confirm that vesamicol inhibits the mobilization of transmitter from a reserve to a more readily releasable pool, and they also suggest that, under these experimental conditions, there might be some futile transmitter mobilization, apparently to sites other than nerve terminal active zones.
Prado
M A
MA
Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada.
Gomez
M V
MV
Collier
B
B
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002415:Cats; D002794:Choline / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D014316:Tritium
D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D012604:Scorpion Venoms; D014316:Tritium; C003609:tityustoxin; C006189:vesamicol; D002794:Choline; D000109:Acetylcholine