Cytosolic calcium oscillations may permit cells to respond to information p
rovided 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 bla
dder epithelial cells. Application of 10 muM acetylcholine or 200 nM bradyk
inin 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 br
adykinin-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-582
3, a highly specific inhibitor of protein kinase G (PKG), suggesting that t
he action of cGMP was mediated by PKG. Comparison of the effect of cGMP wit
h that of xestospongin C, an inhibitor of the inositol 1,4,5-trisphosphate
(IP3) receptor, revealed similarities between the action of cGMP and xestos
pongin C. Therefore, it is likely that cGMP and PKG may target a signal tra
nsduction step(s) linked to IP3 receptor-mediated Ca2+ release.