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Urinary concentrating function in mice lacking EP3 receptors for prostaglandin E2

Urinary concentrating function in mice lacking EP3 receptors for prostaglandin E2 Abstract 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. gene targeting kidney eicosanoids vasopressin Footnotes Address for reprint requests: T. M. Coffman, Room B3002/Nephrology, VA Medical Center, 508 Fulton Street, Durham, NC 27705 These studies were supported by National Institutes of Health Grants DK-38108 and HL-58554 and by the Department of Veterans Affairs. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1998 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Renal Physiology The American Physiological Society

Urinary concentrating function in mice lacking EP3 receptors for prostaglandin E2

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6127
eISSN
1522-1466
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Abstract

Abstract 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. gene targeting kidney eicosanoids vasopressin Footnotes Address for reprint requests: T. M. Coffman, Room B3002/Nephrology, VA Medical Center, 508 Fulton Street, Durham, NC 27705 These studies were supported by National Institutes of Health Grants DK-38108 and HL-58554 and by the Department of Veterans Affairs. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1998 the American Physiological Society

Journal

AJP - Renal Physiology – The American Physiological Society

Published: Dec 1, 1998

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