Characterization of a Rabbit Kidney Prostaglandin F2α Receptor Exhibiting Gi-restricted Signaling That Inhibits Water Absorption in the Collecting Duct

Abstract

PGF 2␣ 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 Prostaglandin F 2␣ is a major prostaglandin excreted in urine (1) and is known to exert potent biological effects via its G protein-coupled cell membrane receptor designated the F-prostanoid (FP) 2 receptor (2-6). FP receptor mRNA is highly expressed along the genitourinary tract including ovary Ͼ uterus and kidney (7-9). Recent studies in mouse kidneys have shown that FP receptor expression is particularly abundant in the distal convoluted tubules and cortical collecting duct (10). The cellular and functional consequences of renal FP receptor activation in these renal epithelia have not been determined. Like PGE 2 (11), intravenous infusion of PGF 2␣ causes both a natriuresis and diuresis (4); however, because high concentrations of PGF 2␣ can cross-activate prostaglandin E 2 -EP3 receptors (12, 13), the molecular basis of PGF 2␣ -associated diuresis remains uncertain. The functional activity of PGE 2 in the rabbit collecting duct epithelium has been elucidated through use of the in vitro microperfused tubule (9, 14 -16); however, the effect of selective FP receptor activation in this segment has not previously been examined. The aim of the present study was to clone the rabbit FP receptor, determine its intrarenal distribution, and elucidate its functional activity in the kidney.

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…It is most abundant in the distal convoluted tubule and aquaporin-2-positive cortical collecting ducts (Saito et al, 2003;Hébert et al, 2005). This distribution is consistent with known FPmediated effects on water and solute transport in these segments of the kidney.…”

Prostanoids in health and disease

“…The FP is highly expressed in the distal convoluted tubules and the cortical collecting duct. In vitro studies suggest that activation of the FP modulates water absorption through inhibition of vasopressin action (17), while infusion of PGF 2a causes both natriuresis and diuresis. Mice with FP deficiency exhibit hypotension, probably due to decreased renin-angiotensin activity (unpublished observations…”

Prostaglandin E2 increases proximal tubule fluid reabsorption, and modulates cultured proximal tubule cell responses via EP1 and EP4 receptors

“…25,26 Microdissected tubules (described above) were transferred to a thermostatically controlled chamber of 1 cm 3 volume and cannulated using concentric micropipettes. Bath solution was continuously exchanged at 0.5 ml/min by infusion pump (Harvard Apparatus, Holliston, MA, USA) and was maintained at 37°C.…”