Urinary concentrating function in mice lacking ep3 receptors for
prostaglandin e2.
Fleming, Eric F., Krairek Athirakul_, Michael I. Oliverio_, Mikelle
Key, Jennifer Goulet, Beverly H. Koller and Thomas M. Coffman_.
Thomas M. Coffman, M.D., Room B3002/Nephrology (111I), VA Medical
Center, 508 Fulton Street, Durham, NC 27705, Telephone: (919) 286
-2947, FAX: (919) 286-6879, e-mail: tcoffman@acpub.duke.edu
APStracts 5:0155F, 1998.
The actions of PGE2 are mediated by four distinct classes of PGE2 (EP)
receptors (EP1-4). However, the in vivo functions of the individual
EP receptor sub-types have not been delineated. In order to study the
functions of one of these, the EP3 receptor, we generated EP3
-deficient mice by gene targeting. EP3 -/- animals survived in
expected numbers, reproduced, and had no obvious abnormalities in
their major organ systems. Because the EP3 receptor is expressed at
high levels in the renal medulla and cortical collecting duct and
previous studies have suggested that the EP3 receptor might
antagonize the effects of vasopressin in the distal nephron, we
examined urinary concentrating functions in EP3 -/- mice. Basal urine
osmolality (UOsm) was similar in groups EP3 -/- and +/+ mice.
However, following inhibition of endogenous PGE2 production by
indomethacin, UOsm increased significantly in wild-type but not EP3
-/- mice. Despite this insensitivity to acute inhibition of prostanoid
production, EP3 -/- mice concentrated and diluted their urine
normally in response to a series of physiological stimuli. This
suggests that PGE2 acts through the EP3 receptor to modulate urinary
concentrating mechanisms in the kidney, but these effects are not
essential for normal regulation of urinary osmolality.
Received 21 April 1998; accepted in final form 31 August 1998.
APS Manuscript Number F90-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998