Role of protein kinase C in the release of [3H]acetylcholine from myenteric plexus treated with vesamicol.
The present experiments investigated the release of [3H]acetylcholine ([3H]ACh) from the guinea pig myenteric plexus treated with 2-(4-phenylpiperidino)cyclohexanol (vesamicol), a drug that impairs ACh accumulation by synaptic vesicles. Ouabain, an Na+-K+ ATPase inhibitor, released [3H]ACh synthesised in the presence of (-)-vesamicol, while electrical field stimulation or KCl depolarisation were not effective to release the transmitter in this condition. The effect of ouabain was Ca2+-dependent and in the presence of (-)-vesamicol it was blocked by calphostin C, an inhibitor of protein kinase C (PKC). In addition, stimulation of kinase C activity by a phorbol ester, but not by its inactive isomer, prevented (-)-vesamicol from interfering with the release of [3H]ACh in electrically-stimulated myenteric plexus, similar to the effect of ouabain. We conclude that release of [3H]ACh induced by ouabain in the presence of (-)-vesamicol depends on PKC activation.
Clarizia
A D
AD
Departamento de Farmacologia, Bioquímica-Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Romano-Silva
M A
MA
Prado
V F
VF
Gomez
M V
MV
Prado
M A
MA
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D014316:Tritium
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D014316:Tritium; C006189:vesamicol; D010042:Ouabain; D011189:Potassium Chloride; D011493:Protein Kinase C; C058819:calphostin C; D000109:Acetylcholine; D002118:Calcium