We have recently reported that bombesin (BBS)-stimulated gastrin release is principally dependent on a Ca2+/calmodulin intracellular pathway, and that it is independent of the cyclic AMP-mediated pathway. Recently it was demonstrated that stimulation of protein kinase C (PK-C) resulted in increased gastrin release from the isolated canine G-cells in cultures. The role of PK-C in the BBS-evoked gastrin release, however, remains unexamined. In this study we examined a possible role of PK-C in the secretion of BBS-stimulated gastrin from isolated perfused rat stomach. The effect of phosphorylation on gastrin release, in response to BBS, was also determined. Administration of phorbol ester (PMA 10-100 nM, a PK-C activator) alone significantly provoked gastrin release, but markedly inhibited the BBS (1 nM) stimulated gastrin secretion in a dose-dependent manner. Molybdic acid (phosphatase inhibitor), caused an enhancement of BBS-evoked gastrin response at doses of 5 or > 5 mM. These results suggest that: (1) diacylglycerol/PK-C pathway may exert a negative feedback control over BBS-induced gastrin release; (2) phosphorylation step is required for gastrin secretion in response to BBS.
- Isolated rat stomach
- Protein kinase C
ASJC Scopus subject areas
- Clinical Biochemistry
- Cellular and Molecular Neuroscience