Characterization of a rabbit kidney prostaglandin F2α receptor exhibiting Gi-restricted signaling that inhibits water absorption in the collecting duct

Abstract

PGF2α 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 (CGD). Although FP receptor activation failed to increase intracellular Ca2+, it potently inhibited vasopressin-stimulated osmotic water permeability (Lp, 10-7 cm/(atm · s)) in in vitro microperfused rabbit CCDs. Inhibition of Lp by the FP selective agonist latanoprost was additive to inhibition of vasopressin action by the EP selective agonist sulprostone. Inhibition of Lp by latanoprost was completely blocked by pertussis toxin, consistent with a uncoupled 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 Ca2+. These studies demonstrate a functional FP receptor on the basolateral membrane of rabbit CCDs. In contrast to the Ca2+ signal transduced by other FP receptors, this renal FP receptor signals via a PT-sensitive mechanism that is not coupled to cell Ca2+. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.