Postsynaptic effects of the phorbol ester TPA on frog end-plates.
The effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a specific activator of protein kinase C (PKc), were examined on the frog neuromuscular junction. The depolarization elicited by iontophoretically applied acetylcholine (ACh) was reversibly decreased by 20-60% when muscle fibres were exposed to 1-5 X 10(-7) M TPA. Liposome-delivered phosphatidylcholine (100 micrograms/ml) prevented this effect. A similar decrease in ACh-sensitivity was produced by diacylglycerol (diolein), a physiological activator of PKc, but in this case the decrease was only partially reversible. In TPA-Ringer, the peak size of miniature end-plate potentials exhibited a small decrease; miniature end-plate currents were reduced in size and their decay time constant became longer and relatively independent of membrane potential. The possibility that these TPA-induced actions are mediated by activation of PKc is discussed.
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000494:pharmacology; D011898:Ranidae; D000077331:Ringer's Solution; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D007552:Isotonic Solutions; D010713:Phosphatidylcholines; D009388:Neostigmine; D000077331:Ringer's Solution; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; C013965:diolein