Acetylcholine synthesis by a sympathetic ganglion in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and picrylsulfonic acid.
The present experiments measured the release and the synthesis of acetylcholine (ACh) by cat sympathetic ganglia in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183 or vesamicol) and/or picrylsulfonic acid (TNBS), two compounds known to have the ability to block the uptake of ACh by cholinergic synaptic vesicles in vitro. We confirmed that, in stimulated (5 Hz) perfused (30 min) ganglia, AH5183 depressed ACh release and ACh tissue content increased by 86 +/- 6% compared to contralateral ganglia used as controls. Preganglionic activity increased ACh release by a similar amount in the presence (19.9 +/- 1.0 pmol/min) or absence (20.5 +/- 2.4 pmol/min) of TNBS. The final tissue ACh content was also similar in the presence (1,668 +/- 166 pmol) or absence (1,680 +/- 56 pmol) of TNBS. However, the AH5183-induced increase of tissue ACh content (86 +/- 6%) was abolished completely when AH5183 was perfused with 1.5 mM TNBS (-3.0 +/- 1.0%). This inhibition of ACh synthesis, observed in TNBS-AH5183-perfused ganglia, was not dependent upon further inhibition of ACh release beyond that caused by AH5183 alone, because 14.0 +/- 1.9% of the transmitter store was released by preganglionic nerve stimulation in the presence of TNBS plus AH5183 and this was similar in the presence of AH5183 without TNBS (14.0 +/- 0.6%). Moreover, when ganglia were first treated with TNBS and then stimulated in the presence of AH5183, an increase of 64 +/- 6% of the ganglionic ACh content occurred, and this increase was not statistically different from the increase measured with AH5183 alone (86 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)
Mykita
S
S
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Collier
B
B
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000818:Animals; D002415:Cats; D002794:Choline / Q000378:metabolism; D004338:Drug Combinations; D004558:Electric Stimulation; D005260:Female; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009578:Nitrobenzenes / Q000494:pharmacology*; D009994:Osmolar Concentration; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D004338:Drug Combinations; D009467:Neuromuscular Depolarizing Agents; D009578:Nitrobenzenes; D010880:Piperidines; C006189:vesamicol; D014302:Trinitrobenzenesulfonic Acid; D010622:Phencyclidine; D002794:Choline; D000109:Acetylcholine