TY - JOUR
T1 - cGMP abolishes agonist-induced [Ca2+]i oscillations in human bladder epithelial cells
AU - Kwan, Hiu Yee
AU - Huang, Yu
AU - Kong, Siu Kai
AU - Yao, Xiaoqiang
N1 - This study was supported by the Hong Kong Research Grant Council (CUHK4079/00M) and the Chinese University Research Committee.
PY - 2001/12
Y1 - 2001/12
N2 - 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 μM 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.
AB - 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 μM 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.
KW - Calcium release
KW - Guanosine 3′,5′-cyclic monophosphate
KW - Inositol 1,4,5-triphosphate
KW - Intracellular calcium concentration
KW - Nitric oxide
KW - Protein kinase G
UR - http://www.scopus.com/inward/record.url?scp=0035662160&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.0031.2001
DO - 10.1152/ajprenal.0031.2001
M3 - Journal article
C2 - 11704557
SN - 1931-857X
VL - 281
SP - F1067-F1074
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 6
ER -