Protein tyrosine kinase inhibitors promote amylase secretion and inhibit ornithine decarboxylase induction in sialagogue-stimulated rat parotid explants

Three sialagogues, isoproterenol (IPR), carbachol, and methoxamine, caused induction of ornithine decarboxylase (ODC) in cultured rat parotid explants. All the protein tyrosine kinase inhibitors tested suppressed this ODC induction but enhanced sialagogue-dependent amylase secretion. Sodium orthovanadate showed the reverse effects as the kinase inhibitors. Immunoblot analysis with anti-phosphotyrosine antibody revealed that herbimycin A depresses IPR-stimulated tyrosine phosphorylation of parotid proteins. Herbimycin A did not affect the IPR- or dibutyryl cAMP-induced surge of the parotid cAMP level but inhibited these agonist-dependent ODC inductions. These results suggest that sialagogue-induced ODC induction and amylase secretion are mediated by different signal transduction pathways and that protein tyrosine kinase participates in IPR-dependent ODC induction and amylase secretion in the process subsequent to the cAMP surge. (C) 1996 Academic Press, Inc.