Saad Adel H, Shimamoto Chikao, Nakahari Takashi, Fujiwara Shoko, Katsu Ken-ichi, Marunaka Yoshinori
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1138-48. doi: 10.1152/ajpgi.00357.2005. Epub 2006 Jan 19.
In guinea pig antral mucous cells, ACh stimulates the Ca(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(2+) mobilization or cAMP accumulation. The Ca(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(2+)-regulated exocytosis, but not the Ca(2+) sensitivity. Moreover, under a condition of ATP depletion by dinitrophenol (DNP) or anoxia (N(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(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(2+)-regulated exocytosis stimulated by ACh.
在豚鼠胃窦黏液细胞中，乙酰胆碱（ACh）刺激钙（Ca²⁺）调节的胞吐作用，其具有一个特征：一个初始的瞬态阶段，随后是一个持续阶段。利用视频显微镜研究了环鸟苷酸（cGMP）对豚鼠胃窦黏液细胞中ACh刺激的胞吐作用的影响。cGMP增加了ACh刺激的胞吐事件的频率，而在未受ACh刺激的条件下，单独的cGMP不会诱导任何胞吐事件。cGMP既不刺激Ca²⁺动员，也不刺激环磷酸腺苷（cAMP）积累。Ca²⁺剂量反应研究表明，cGMP使剂量反应曲线向上移动，而不向较低浓度方向移动。这表明cGMP增加了Ca²⁺调节的胞吐作用的最大反应性，但不增加Ca²⁺敏感性。此外，在二硝基苯酚（DNP）使ATP耗竭或缺氧（用氮气鼓泡）的条件下，ACh仅诱发胞吐事件的持续阶段，而无初始瞬态阶段。然而，在ATP耗竭前加入cGMP时，ACh诱发一个初始瞬态阶段，随后是一个持续阶段，而在ATP耗竭后加入cGMP的情况下，仅诱发一个持续阶段。因此，cGMP诱导的ACh刺激的胞吐事件增强需要ATP，这表明cGMP调节胃窦黏液细胞中Ca²⁺调节的胞吐作用的ATP依赖性启动。总之，cGMP通过加速ATP依赖性启动增加了准备好的颗粒数量，从而增强了ACh刺激的Ca²⁺调节的胞吐作用。
