cAMP modulation of Ca2+-regulated exocytosis in ACh-stimulated antral mucous cells of guinea pig

Abstract

Effects of cAMP accumulation on ATP-dependent priming and Ca2+-dependent fusion in Ca2+-regulated exocytosis were examined in antral mucous cells of guinea pigs by using video-enhanced contrast microscopy. The Ca2+-regulated exocytosis activated by 1 μM ACh consisted of two phases, an initial transient phase followed by a sustained phase, which were potentiated by cAMP accumulation. Depletion of ATP by 100 μM dinitrophenol (uncoupler of oxidative phosphorylation) or anoxia induced the sustained phase without the initial transient phase in Ca2+-regulated exocytosis. However, accumulation of cAMP before depletion of ATP induced and potentiated an initial transient phase followed by a sustained phase in Ca2+-regulated exocytosis. This suggests that the initial transient phase of Ca2+-regulated exocytosis is induced by fusion of all primed granules maintained by ATP and that accumulation of cAMP accelerates ATP-dependent priming of the exocytotic cycle. Moreover, ACh and Ca2+ dose-response studies showed that accumulation of cAMP shifted the dose-response curves to the low concentration side, suggesting that it increases Ca2+ sensitivity in the fusion of the exocytotic cycle. In conclusion, cAMP accumulation increases the number of primed granules and Ca2+ sensitivity of the fusion, which potentiates Ca2+-regulated exocytosis in antral mucous cells.