Biphasic effect of phorbol myristate acetate on histamine secretion induced by compound 48/80 in rat peritoneal mast cells.
Rat peritoneal mast cells which had been preincubated with phorbol myristate acetate (PMA, 100 ng/ml) for 30 sec elicited an enhanced histamine secretion induced by a potent secretagogue, compound 48/80. But a longer (5 min) preincubation with PMA followed by the agonist-stimulation induced a suppressed histamine secretion. A 5 min-PMA-pretreatment inhibited the compound 48/80-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in [32P]-labeled cells. PMA-treatment alone for 5 min induced an activation of Ca2+-efflux monitored by 45Ca2+. The inhibition of histamine secretion induced by a 5 min-PMA-pretreatment followed by the agonist-stimulation may partly be attributed to the decreased intracellular Ca2+ concentration, [Ca2+]i, probably due to the depressed PIP2 breakdown and enhanced Ca2+-efflux. On the other hand, a 30 sec-preincubation with PMA followed by compound 48/80-stimulation induced a slight but significant increase in histamine secretion. In this case, neither breakdown of PIP2 nor Ca2+-influx was enhanced to raise the [Ca2+]i. Although we are unable to explain the mechanism for the enhancement of histamine secretion by a short (30 sec) PMA-preincubation, these results suggest that the biphasic effects of PMA on histamine secretion are mediated by intracellular Ca2+ mobilization probably via protein kinase C activation.
D000818:Animals; D002118:Calcium / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D008407:Mast Cells / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D010704:Phorbols; D003189:p-Methoxy-N-methylphenethylamine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium