title: Regulation of urea permeability in frog urinary bladder by prostaglandin E(2).
abstract: The present study was performed to investigate the role of prostaglandin E(2) (PGE(2)) in the regulation of urea transport in the frog urinary bladder, which is known to occur via a specialized arginine-vasotocin- (AVT-) regulated urea transporter. The bladders isolated from Rana temporaria L. were filled with amphibian Ringer solution containing 370 Bq/ml (0.01 microCi/ml) of [14C]urea, and urea permeability ( P(urea)) was determined by sampling the serosal and mucosal bathing medium at 30-min intervals for measurement of radioactivity. It was found that, from the serosal side, PGE(2) (10 nM to 1 microM) caused a dose-dependent increase in P(urea) [(7.2+/-1.8)x10(-6) cm/s in the presence of 0.5 microM PGE(2)versus (1.0+/-0.2)x10(-6) cm/s in control, n=9, P<0.001]. As in response to AVT, the PGE(2)-induced P(urea)reached a maximum in 1-1.5 h after the agonist was added. The stimulatory effects of PGE(2) and AVT applied together were not additive. PGE(2)-induced urea transport was strongly inhibited by nearly 75% in the presence of mucosal or serosal phloretin (10(-4) M). P(urea) was enhanced up to (4.7+/-0.8)x10(-6) cm/s (n=12, P<0.001) by butaprost (5 x 10(-6) M), a selective EP(2) receptor agonist, while sulprostone (EP(1)/EP(3) agonist, 10(-6) M) caused no changes in P(urea). PGE(2)dose-dependently increased the content of cAMP in mucosal epithelial cells (control: 18.0+/-1.8; 10(-6) M PGE(2): 74.2+/-9.3 pmol cAMP/mg protein per 30 min, n=7, P<0.001). Phorbol esters did not alter PGE(2)-induced P(urea), whereas H-89 (20 microM), a protein kinase A inhibitor, reduced it by 45.1+/-9.9% ( n=5, P<0.05). PGE(2)did not change the AVT-stimulated P(urea) measured in isoosmotic conditions, but inhibited the last one in the presence of a serosa-to-mucosa osmotic gradient. The data obtained show that, in the frog urinary bladder, PGE(2)is a stimulator of phloretin-inhibitable urea transport. Its effect seems to be mediated by EP(2) receptor-coupled generation of intracellular cAMP.
authors.affiliation: Laboratory of Kidney Physiology, Sechenov Institute of Evolutionary Physiology and Biochemistry, 44, M.Thorez Av., 194223 Saint-Petersburg, Russia.
authors.forename: Vera T
authors.initials: VT
authors.lastname: Bachteeva
authors.forename: Ekaterina M
authors.initials: EM
authors.lastname: Fock
authors.forename: Elena A
authors.initials: EA
authors.lastname: Lavrova
authors.forename: Elena V
authors.initials: EV
authors.lastname: Naboka
authors.forename: Rimma G
authors.initials: RG
authors.lastname: Parnova
mesh_terms: D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D010693:Phloretin / Q000494:pharmacology; D011896:Rana temporaria; D011982:Receptors, Prostaglandin / Q000819:agonists; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014508:Urea / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D014668:Vasotocin / Q000494:pharmacology
chemical_list: D007202:Indicators and Reagents; D007546:Isoquinolines; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D014508:Urea; D000242:Cyclic AMP; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D010693:Phloretin; D014668:Vasotocin