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 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.