Characterization of a rabbit kidney prostaglandin F(2{alpha}) receptor exhibiting G(i)-restricted signaling that inhibits water absorption in the collecting duct.

H├ębert RL, Carmosino M, Saito O, Yang G, Jackson CA, Qi Z, Breyer RM, Natarajan C, Hata AN, Zhang Y, Guan Y, Breyer MD
J Biol Chem. 2005 280 (41): 35028-37

PMID: 16096282 · DOI:10.1074/jbc.M505852200

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+).

MeSH Terms (35)

Amino Acid Sequence Animals Base Sequence Calcium Cell Line Cloning, Molecular Dinoprost DNA, Complementary Female Genetic Vectors GTP-Binding Protein alpha Subunits, Gi-Go Humans In Situ Hybridization Kidney Kidney Tubules, Collecting Lac Operon Latanoprost Ligands Molecular Sequence Data Ovary Perfusion Pertussis Toxin Prostaglandins Prostaglandins F, Synthetic Protein Binding Rabbits Reverse Transcriptase Polymerase Chain Reaction Ribonucleases RNA, Messenger Sequence Homology, Amino Acid Signal Transduction Time Factors Tissue Distribution Transfection Water

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