Submitted on November 17, 2006
Accepted on March 9, 2007
Prostaglandin E2 inhibits vasotocin-induced osmotic water permeability in the frog urinary bladder by EP1-receptor-mediated activation of NO/cGMP pathway
Vera Bachteeva1, Ekaterina Fock1, Elena Lavrova1, Svetlana Nikolaeva1, Stepan Gambaryan2*, and Rimma Parnova1
1 Russian Academy of Sciences, I.M. Sechenov Institute of Evolutionary Physiology & Biochemistry, St. Petresburg, Russian Federation
2 University of Wuerzburg, Institute of Clinical Biochemistry and Pathobiochemistry, Wuerzburg, Germany; Russian Academy of Sciences, I.M. Sechenov Institute of Evolutionary Physiology & Biochemistry, St. Petresburg, Russian Federation
* To whom correspondence should be addressed. E-mail: gambaryan{at}klin-biochem.uni-wuerzburg.de.
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 NO in epithelial cells. It was shown that the inhibitory effect of 17-phenyl-trinor-PGE2 (17-ph-PGE2), EP1 agonist, on AVT-induced OWP was significantly reduced in the presence of 7-nitroindazole (7-NI), nNOS inhibitor. NOS activity both in lysed and intact epithelial cells measured as a rate of convertion of L-[3H]-arginine to L-[3H]-citrullin was Ca2+-dependent and was 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, EP1 antagonist. 7-NI reduced the stimulatory effect of 17-ph-PGE2 on NOS activity. 17-ph-PGE2 increased [Ca2+]i. 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 crosstalk between AVT, PGE2, and nNOS that may be important in the regulation of water transport.
