cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

In guinea pig antral mucous cells, ACh stimulates the [Ca.sup.2+]-regulated exocytosis, which has a characteristics feature: an initial transient phase followed by a sustained phase. The effects of cGMP on ACh-stimulated exocytosis were studied in guinea pig antral mucous cells using video microscopy. cGMP enhanced the frequency of ACh-stimulated exocytotic events, whereas cGMP alone did not induce any exocytotic events under the ACh-unstimulated condition, cGMP did not stimulate either [Ca.sup.2+] mobilization or cAMP accumulation. The [Ca.sup.2+] dose-response studies demonstrated that cGMP shifted the dose-response curve upward with no shift to the lower concentration. This indicates that cGMP increased maximal responsiveness of the [Ca.sup.2+]-regulated exocytosis, but not the [Ca.sup.2+] sensitivity. Moreover, under a condition of ATP depletion by dinitrophenol (DNP) or anoxia ([N.sub.2] bubbling), ACh evoked only a sustained phase in exocytotic events with no initial transient phase. However, ACh evoked an initial transient phase followed by a sustained phase with addition of cGMP before ATP depletion, whereas only a sustained phase was evoked in a case of cGMP addition after ATP depletion. Thus cGMP-induced enhancement in ACh-stimulated exocytotic events requires ATP, suggesting that cGMP modulates ATP-dependent priming of [Ca.sup.2+]-regulated exocytosis in antral mucous cells. In conclusion, cGMP increases the number of primed granules via acceleration of the ATP-dependent priming, which enhances the [Ca.sup.2+]-regulated exocytosis stimulated by ACh. gastric mucin secretion; guanosine 3'-cyclic monophosphate; exocytosis; acetylcholine; intracellular calcium concentration