Phorbol ester-induced protein secretion in rat parotid gland. Relationship to the role of inositol lipid breakdown and protein kinase C activation in stimulus-secretion coupling.
When added to rat parotid gland slices incubated in vitro, 4 alpha-phorbol-dibutyrate (PDBu) induced a dose-dependent increase in protein secretion, but did not affect membrane permeability to K+ (as determined by 86Rb efflux). The response to PDBu was unaffected by the removal of extracellular Ca2+ and was not markedly potentiated by incubation with the phosphodiesterase inhibitor, methylisobutylxanthine. PDBu did not activate phospholipase C breakdown of inositol lipids as shown by a failure to increase formation of soluble inositol phosphates. When applied in combination with the Ca2+ ionophore, ionomycin, a secretory rate was obtained that was greater than the predicted sum of rates obtained when the two drugs were given alone. These results, when taken with the reported results of others, are consistent with an action of PDBu in activating protein kinase C and suggest that this enzyme plays an important role in the pathway linking receptor activation to protein secretion, but not K+ flux, in the parotid gland.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism*; D015759:Ionomycin; D007700:Kinetics; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D014316:Tritium
D002273:Carcinogens; D004987:Ethers; D008688:Methacholine Compounds; D010703:Phorbol Esters; D010704:Phorbols; D011506:Proteins; D016210:Methacholine Chloride; D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; D007294:Inositol; D004533:Egtazic Acid; D015759:Ionomycin; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium