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

Abstract

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 of 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 2 drugs were given alone. Evidently, PDBu activates protein kinase C and this enzyme plays an important role in the pathway linking receptor activation to protein secretion, but not K+ flux, in the parotid gland.