Stimulation of renin release by prostaglandin E(2) is mediated by EP(2) and EP(4) receptors in mouse kidneys

Schweda, Frank and Klar, Juergen and Narumiya, Shuh and Nuesing, Rolf M. and Kurtz, Armin (2004) Stimulation of renin release by prostaglandin E(2) is mediated by EP(2) and EP(4) receptors in mouse kidneys. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 287 (3). F427-F433. ISSN 1931-857X,

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Abstract

PGE(2) is a potent stimulator of renin release. So far, the contribution of each of the four PGE(2) receptor subtypes (EP(1) - EP(4)) in the regulation of renin release has not been characterized. Therefore, we investigated the effects PGE2 on renin secretion rates (RSR) from isolated, perfused kidneys of EP(1)(-/-), EP(2)(-/-), EP(3)(-/-), EP(4)(-/-), and wild-type mice. PGE(2) concentration dependently stimulated RSR from kidneys of all four knockout strains with a threshold concentration of 1 nM in EP(1)(-/-), EP(2)(-/-), EP(3)(-/-), and wild-type mice, whereas the threshold concentration was shifted to 10 nM in EP(4)(-/-) mice. Moreover, the maximum stimulation of RSR by PGE(2) at 1 muM was significantly reduced in EP(4)(-/-) (12.8-fold of control) and EP(2)(-/-) (15.9-fold) compared with wild-type (20.7-fold), EP(1)(-/-) (23.8-fold), and EP(3)(-/-) (20.1-fold). In contrast, stimulation of RSR by either the loop diuretic bumetanide or the beta-adrenoceptor agonist isoproterenol was similar in all strains. PGE2 exerted a dual effect on renal vascular tone, inducing vasodilatation at low concentrations ( 1 nmol/) and vasoconstriction at higher concentrations ( 100 nmol/) in kidneys of wild-type mice. In kidneys of EP(2)(-/-) as well as EP(4)(-/-) mice, vasodilatation at low PGE(2) concentrations was prevented, whereas vasoconstriction at higher concentrations was augmented. In contrast, the vasodilatatory component was pronounced in kidneys of EP(1) and EP(3) knockout mice, whereas in both genotypes the vasoconstriction at higher PGE(2) concentrations was markedly blunted. Our data provide evidence that PGE(2) stimulates renin release via activation of EP(2) and EP(4) receptors, whereas EP(1) and EP(3) receptors appear to be without functional relevance in juxtaglomerular cells. In contrast, all four receptor subtypes are involved in the control of renal vascular tone, EP(1) and EP(3) receptors increasing, and EP(2) as well as EP(4) receptors, decreasing it.

Item Type: Article
Uncontrolled Keywords: RENAL CORTICAL SLICES; MACULA DENSA; BLOOD-PRESSURE; RENOVASCULAR HYPERTENSION; ACE-INHIBITION; MICE LACKING; RAT-KIDNEY; CYCLOOXYGENASE-2; SECRETION; EXPRESSION; renin secretion; renal vascular resistance; bumetanide; isolated; perfused mouse kidney
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda
Depositing User: Dr. Gernot Deinzer
Date Deposited: 28 Jun 2021 10:19
Last Modified: 28 Jun 2021 10:19
URI: https://pred.uni-regensburg.de/id/eprint/37199

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