The prostaglandin E2 analogue sulprostone antagonizes vasopressin-induced antidiuresis through activation of Rho.
Arginine-vasopressin (AVP) facilitates water reabsorption in renal collecting duct principal cells by activation of vasopressin V2 receptors and the subsequent translocation of water channels (aquaporin-2, AQP2) from intracellular vesicles into the plasma membrane. Prostaglandin E2 (PGE2) antagonizes AVP-induced water reabsorption; the signaling pathway underlying the diuretic response is not known. Using primary rat inner medullary collecting duct (IMCD) cells, we show that stimulation of prostaglandin EP3 receptors induced Rho activation and actin polymerization in resting IMCD cells, but did not modify the intracellular localization of AQP2. However, AVP-, dibutyryl cAMP- and forskolin-induced AQP2 translocation was strongly inhibited. This inhibitory effect was independent of increases in cAMP and cytosolic Ca2+. In addition, stimulation of EP3 receptors inhibited the AVP-induced Rho inactivation and the AVP-induced F-actin depolymerization. The data suggest that the signaling pathway underlying the diuretic effects of PGE2 and probably those of other diuretic agents include cAMP- and Ca2+-independent Rho activation and F-actin formation.
Tamma
Grazia
G
Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-Buch, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Wiesner
Burkhard
B
Furkert
Jens
J
Hahm
Daniel
D
Oksche
Alexander
A
Schaefer
Michael
M
Valenti
Giovanna
G
Rosenthal
Walter
W
Klussmann
Enno
E
D000199:Actins / Q000378:metabolism; D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D007679:Kidney Medulla / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009481:Neurophysins / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism; D015398:Signal Transduction; D014667:Vasopressins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
C438657:AVP protein, human; D000199:Actins; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D009481:Neurophysins; D011448:Prostaglandin Antagonists; D011498:Protein Precursors; D018078:Receptors, Prostaglandin E; D017483:Receptors, Vasopressin; D014667:Vasopressins; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D005576:Colforsin; C016767:sulprostone; D000242:Cyclic AMP; D020741:rho GTP-Binding Proteins; D015232:Dinoprostone