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Am J Physiol Regul Integr Comp Physiol 293: R528-R537, 2007. First published March 15, 2007; doi:10.1152/ajpregu.00811.2006
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WATER AND ELECTROLYTE HOMEOSTASIS

Prostaglandin E2 inhibits vasotocin-induced osmotic water permeability in the frog urinary bladder by EP1-receptor-mediated activation of NO/cGMP pathway

Vera Bachteeva,1 Ekaterina Fock,1 Elena Lavrova,1 Svetlana Nikolaeva,1 Stepan Gambaryan,2 and Rimma Parnova1

1Laboratory of Renal Physiology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia; and 2Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany

Submitted 17 November 2006 ; accepted in final form 9 March 2007

PGE2 is a well-known inhibitor of the antidiuretic hormone-induced increase of osmotic water permeability (OWP) in different osmoregulatory epithelia; however, the mechanisms underlying this effect of PGE2 are not completely understood. Here, we report that, in the frog Rana temporaria urinary bladder, EP1-receptor-mediated inhibition of arginine-vasotocin (AVT)-induced OWP by PGE2 is attributed to increased generation of nitric oxide (NO) in epithelial cells. It was shown that the inhibitory effect of 17-phenyl-trinor-PGE2 (17-ph-PGE2), an EP1 agonist, on AVT-induced OWP was significantly reduced in the presence of 7-nitroindazole (7-NI), a neuronal NO synthase (nNOS) inhibitor. NO synthase (NOS) activity in both lysed and intact epithelial cells measured as a rate of conversion of L-[3H]arginine to L-[3H]citrulline was Ca2+ dependent and inhibited by 7-NI. PGE2 and 17-ph-PGE2, but not M&B-28767 (EP3 agonist) or butaprost (EP2 agonist), stimulated NOS activity in epithelial cells. The above effect of PGE2 was abolished in the presence of SC-19220, an EP1 antagonist. 7-NI reduced the stimulatory effect of 17-ph-PGE2 on NOS activity. 17-ph-PGE2 increased intracellular Ca2+ concentration and cGMP in epithelial cells. Western blot analysis revealed an nNOS expression in epithelial cells. These results show that the inhibitory effect of PGE2 on AVT-induced OWP in the frog urinary bladder is based at least partly on EP1-receptor-mediated activation of the NO/cGMP pathway, suggesting a novel cross talk between AVT, PGE2, and nNOS that may be important in the regulation of water transport.

amphibian urinary bladder; nitric oxide; neuronal nitric oxide synthase



Address for reprint requests and other correspondence: R. Parnova, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, M. Torez Av., 44, 194223 St. Petersburg, Russia (e-mail: parnova{at}iephb.ru); or S. Gambaryan, Institute of Clinical Biochemistry and Pathobiochemistry, Univ. of Würzburg, Grombuehlstr. 12, 97080 Würzburg, Germany (e-mail: gambaryan{at}klin-biochem.uni-wuerzburg.de)







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