Cyclic GMP modulates ACh-stimulated exocytosis in guinea pig antral mucous cells

Abstract

In guinea pig antral mucous cells, acetylcholine (ACh) induces a biphasic increase in the Ca²⁺-regulated exocytosis: an initial transient phase followed by a sustained one. We studied the effects of cGMP on ACh-stimulated exocytosis in guinea pig antral mucous cells using video microscopy. Cyclic GMP enhanced the frequency of ACh-stimulated exocytotic events, while cGMP alone induced no exocytotic events under the ACh-unstimulated condition. Cyclic GMP did not affect either Ca²⁺ mobilization or cAMP accumulation. cGMP shifted the Ca²⁺ dose-response curve upward with no shift to the lower-concentration, indicating that cGMP increases responsibility of the Ca²⁺-regulated exocytosis, but not the Ca²⁺ sensitivity. When cGMP was added after ATP depletion by dinitrophenol (DNP) or anoxia (N₂ bubbling), ACh evoked only a sustained phase in the exocytosis without any initial transient phase. In contrast, when cells were pretreated with cGMP before ATP depletion, ACh evoked the biphasic exocytotic events. These observations indicate that cGMP modulates ATP dependent priming of Ca²⁺-regulated exocytotic events. In conclusion, cGMP increases the number of primed granules via acceleration of the ATP-dependent priming step, which enhances the Ca²⁺-regulated exocytotic events stimulated by ACh. [J Physiol Sci. 2006;56 Suppl:S111]