Аннотация:The actions of prostaglandin (PG) E 2 are mediated by four distinct classes of PGE 2 E-prostanoid (EP) receptors (EP 1 through EP 4 ). However, the in vivo functions of the individual EP receptor subtypes have not been delineated. To study the functions of one of these subtypes, the EP 3 receptor, we generated EP 3 -deficient (−/−) mice by gene targeting. EP 3 −/− animals survived in expected numbers, reproduced, and had no obvious abnormalities in their major organ systems. Because the EP 3 receptor is expressed at high levels in the renal medulla and cortical collecting duct, and because previous studies have suggested that the EP 3 receptor might antagonize the effects of vasopressin in the distal nephron, we examined urinary concentrating functions in EP 3 −/− mice. Basal urine osmolality (U Osm ) was similar in groups of EP 3 −/− and wild-type (EP 3 +/+) mice. However, after inhibition of endogenous PGE 2 production by indomethacin, U Osm increased significantly in EP 3 +/+ but not in EP 3 −/− mice. Despite this insensitivity to acute inhibition of prostanoid production, EP 3 −/− mice concentrated and diluted their urine normally in response to a series of physiological stimuli. This suggests that PGE 2 acts through the EP 3 receptor to modulate urinary concentrating mechanisms in the kidney, but these effects are not essential for normal regulation of urinary osmolality.
