Prostaglandin E2 inhibits vasotocin-induced osmotic water permeability in the frog urinary bladder by EP1-receptor-mediated activation of NO/cGMP pathway.
PGE(2) 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 PGE(2) are not completely understood. Here, we report that, in the frog Rana temporaria urinary bladder, EP(1)-receptor-mediated inhibition of arginine-vasotocin (AVT)-induced OWP by PGE(2) is attributed to increased generation of nitric oxide (NO) in epithelial cells. It was shown that the inhibitory effect of 17-phenyl-trinor-PGE(2) (17-ph-PGE(2)), an EP(1) 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-[(3)H]arginine to l-[(3)H]citrulline was Ca(2+) dependent and inhibited by 7-NI. PGE(2) and 17-ph-PGE(2), but not M&B-28767 (EP(3) agonist) or butaprost (EP(2) agonist), stimulated NOS activity in epithelial cells. The above effect of PGE(2) was abolished in the presence of SC-19220, an EP(1) antagonist. 7-NI reduced the stimulatory effect of 17-ph-PGE(2) on NOS activity. 17-ph-PGE(2) increased intracellular Ca(2+) concentration and cGMP in epithelial cells. Western blot analysis revealed an nNOS expression in epithelial cells. These results show that the inhibitory effect of PGE(2) on AVT-induced OWP in the frog urinary bladder is based at least partly on EP(1)-receptor-mediated activation of the NO/cGMP pathway, suggesting a novel cross talk between AVT, PGE(2), and nNOS that may be important in the regulation of water transport.
Bachteeva
Vera
V
Laboratory of Renal Physiology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, M. Torez Avenue 44, 194223 St. Petersburg, Russia.
Fock
Ekaterina
E
Lavrova
Elena
E
Nikolaeva
Svetlana
S
Gambaryan
Stepan
S
Parnova
Rimma
R
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011896:Rana temporaria; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015398:Signal Transduction / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism*; D014668:Vasotocin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
C092396:17-phenyltrinorprostaglandin E2; D004791:Enzyme Inhibitors; D007191:Indazoles; D010120:Oxytocics; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D009569:Nitric Oxide; D000242:Cyclic AMP; D052248:Nitric Oxide Synthase Type I; D015232:Dinoprostone; D002118:Calcium; C080122:7-nitroindazole; D014668:Vasotocin