cGMP abolishes agonist-induced [Ca2+]i oscillations in human bladder epithelial cells

Cytosolic calcium oscillations may permit cells to respond to information provided by increases in intracellular Ca2+ concentration ([Ca2+](i)) while avoiding prolonged exposure to constantly elevated [Ca2+](i). In this study, we demonstrated that agonists could induce Ca2+ oscillations in human bladder epithelial cells. Application of 10 muM acetylcholine or 200 nM bradykinin triggered an initial Ca2+ transient that was followed by periodic [Ca2+](i) oscillations. The oscillations did not depend on extracellular Ca2+. 8-Bromoguanosine 3', 5'-cyclic monophosphate abolished acetylcholine- or bradykinin-induced oscillations. Elevation of cellular cGMP by dipyridamole, an inhibitor of cGMP-specific phosphodiesterase, also terminated the [Ca2+](i) oscillations. The inhibitory effect of cGMP could be reversed by KT-5823, a highly specific inhibitor of protein kinase G (PKG), suggesting that the action of cGMP was mediated by PKG. Comparison of the effect of cGMP with that of xestospongin C, an inhibitor of the inositol 1,4,5-trisphosphate (IP3) receptor, revealed similarities between the action of cGMP and xestospongin C. Therefore, it is likely that cGMP and PKG may target a signal transduction step(s) linked to IP3 receptor-mediated Ca2+ release.