cGMP abolishes agonist-induced [Ca(2+)](i) oscillations in human bladder epithelial cells.
Cytosolic calcium oscillations may permit cells to respond to information provided by increases in intracellular Ca(2+) concentration ([Ca(2+)](i) ) while avoiding prolonged exposure to constantly elevated [Ca(2+)](i). In this study, we demonstrated that agonists could induce Ca(2+) oscillations in human bladder epithelial cells. Application of 10 microM acetylcholine or 200 nM bradykinin triggered an initial Ca(2+) transient that was followed by periodic [Ca(2+)](i) oscillations. The oscillations did not depend on extracellular Ca(2+). 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 [Ca(2+)](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 (IP(3)) 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 IP(3) receptor-mediated Ca(2+) release.
Kwan
H Y
HY
Department of Physiology, Chinese University of Hong Kong, Hong Kong, China.
Huang
Y
Y
Kong
S K
SK
Yao
X
X
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002227:Carbazoles; D002460:Cell Line; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004176:Dipyridamole / Q000494:pharmacology; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007211:Indoles; D007700:Kinetics; D047028:Macrocyclic Compounds; D010080:Oxazoles / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology* / Q000378:metabolism*
D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D047028:Macrocyclic Compounds; D010080:Oxazoles; D010726:Phosphodiesterase Inhibitors; C108644:xestospongin A; C073601:KT 5823; C016276:8-bromocyclic GMP; D004176:Dipyridamole; D017869:Cyclic GMP-Dependent Protein Kinases; D000252:Calcium-Transporting ATPases; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin