Phorbol esters induce neurotransmitter release in cholinergic synaptosomes from Torpedo electric organ.
The effect of phorbol esters and so the involvement of Ca2+/phospholipid-dependent protein kinase (protein kinase C;PKC) in the release of acetylcholine (ACh) was studied using Torpedo electric organ synaptosomes. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a known activator of PKC, induced neurotransmitter release in a concentration-dependent manner and increased the potassium-evoked release of ACh. The effect of TPA was shown to be independent of the extrasynaptosomal calcium concentration. TPA-induced ACh release was reversed by H-7, an inhibitor of PKC activity. This drug showed no effect on potassium-evoked ACh release. Botulinum toxin, a strong blocker of potassium-induced ACh release in that synaptosomal preparation, showed no inhibitory effect on the TPA-induced ACh release. Our results suggest that activation of PKC potentiates the release of an ACh pool that is not releasable by potassium depolarization, independently of the extracellular calcium concentration.
Guitart
X
X
Departament de Biologia Cellular i Anatomía Patològica, Facultat de Medicina, Universitat de Barcelona, Spain.
Marsal
J
J
Solsona
C
C
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004557:Electric Organ / Q000378:metabolism* / Q000648:ultrastructure; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013574:Synaptosomes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology; D014101:Torpedo
D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D001905:Botulinum Toxins; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate