Characterization of a rabbit kidney prostaglandin F(2{alpha}) receptor exhibiting G(i)-restricted signaling that inhibits water absorption in the collecting duct.
PGF(2alpha) is the most abundant prostaglandin detected in urine; however, its renal effects are poorly characterized. The present study cloned a PGF-prostanoid receptor (FP) from the rabbit kidney and determined the functional consequences of its activation. Nuclease protection assay showed that FP mRNA expression predominates in rabbit ovary and kidney. In situ hybridization revealed that renal FP expression predominates in the cortical collecting duct (CCD). Although FP receptor activation failed to increase intracellular Ca(2+), it potently inhibited vasopressin-stimulated osmotic water permeability (L(p), 10(-7) cm/(atm.s)) in in vitro microperfused rabbit CCDs. Inhibition of L(p) by the FP selective agonist latanoprost was additive to inhibition of vasopressin action by the EP selective agonist sulprostone. Inhibition of L(p) by latanoprost was completely blocked by pertussis toxin, consistent with a G(i)-coupled mechanism. Heterologous transfection of the rabbit FPr into HEK293 cells also showed that latanoprost inhibited cAMP generation via a pertussis toxin-sensitive mechanism but did not increase cell Ca(2+). These studies demonstrate a functional FP receptor on the basolateral membrane of rabbit CCDs. In contrast to the Ca(2+) signal transduced by other FP receptors, this renal FP receptor signals via a PT-sensitive mechanism that is not coupled to cell Ca(2+).
Hébert
Richard L
RL
Departments of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
Carmosino
Monica
M
Saito
Osamu
O
Yang
Guangrui
G
Jackson
Cynthia A
CA
Qi
Zhonghua
Z
Breyer
Richard M
RM
Natarajan
Chandramohan
C
Hata
Aaron N
AN
Zhang
Yahua
Y
Guan
Youfei
Y
Breyer
Matthew D
MD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015237:Dinoprost / Q000737:chemistry / Q000502:physiology*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D007763:Lac Operon; D000077338:Latanoprost; D008024:Ligands; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism; D010477:Perfusion; D037342:Pertussis Toxin / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014867:Water / Q000378:metabolism*
D018076:DNA, Complementary; D008024:Ligands; D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D014867:Water; D000077338:Latanoprost; D015237:Dinoprost; D037342:Pertussis Toxin; D012260:Ribonucleases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium