The roles of calmodulin and protein kinase C in histamine secretion from mast cells.
The effect of a new calmodulin-antagonist, 5-iodo-1-C8, with a high selectivity for calmodulin in comparison to protein kinase C, has been investigated on histamine secretion from mast cells. It has been found to be much more sensitive for the inhibition of histamine secretion than the earlier calmodulin-antagonists, trifluoperazine and W7. The effect of four inhibitors of protein kinase C, viz. staurosporine, K252a, tamoxifen and sphingosine, has also been studied on histamine secretion from mast cells. All of them caused dose-dependent inhibition of histamine secretion induced by the three secretagogues used: antigen, compound 48/80 and the calcium ionophore A23187. K252a was tested against histamine release, induced by the stimulation of protein kinase C alone with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) or the synthetic diacylglycerol, 1-oleoyl-2-acetyl-rac-glycerol (OAG). In both the cases K252a caused dose-dependent inhibition of histamine release. Staurosporine was also tested against TPA and was found to inhibit the release induced by it. Potentiation and inhibition (modulation) of secretagogue-induced histamine release by simultaneous protein kinase C stimulation with TPA or OAG have been demonstrated before. The potentiation and inhibition are shown to be antagonized by staurosporine. The observations point to the involvement of both calmodulin and protein kinase C in the histamine secretion process from mast cells.
Chakravarty
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Department of Pharmacology, Odense University, Denmark.
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D004075:Diglycerides / Q000494:pharmacology; D006636:Histamine Release / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002147:Calmodulin; D004075:Diglycerides; D013449:Sulfonamides; C064991:N-(8-aminohexyl)-5-iodonaphthalene-1-sulfonamide; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate