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1 Institute for Physiology, University of Regensburg, Regensburg, Germany
2 Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan
3 Department of Pediatrics, Philipps University, Marburg, Germany
* To whom correspondence should be addressed. E-mail: frank.schweda{at}klinik.uni-regensburg.de.
ProstaglandinE2 (PGE2) is a potent stimulator of renin release. So far the contribution of each of the four PGE2 receptor subtypes (EP1-EP4) 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 EP1-/-, EP2-/- EP3-/- and EP4-/- mice and their wildtypes. PGE2 concentration dependently stimulated RSR from kidneys of all four knockout strains with a threshold concentration of 1nmol/L in EP1-/-, EP2-/-, EP3-/- and wildtype mice, while the threshold concentration was shifted to 10nmol/L in EP4-/- mice. Moreover, the maximum stimulation of RSR by PGE2 at 1µmol/L was significantly reduced in EP4-/- (12.8-fold of control) and EP2 -/- (15.9-fold) compared to wildtypes (20.7-fold), EP1-/- (23.8-fold) and EP3-/- (20.1-fold). In contrast, stimulation of RSR by either the loop diuretic bumetanide or the 
-adrenoceptor agonist isoproterenol was similar in all strains. PGE2 exerted a dual effect on renal vascular tone, inducing vasodilatation at low concentrations (1nmol/L) and vasoconstriction at higher concentrations (100nmol/L) in kidneys of wildtype mice. In kidneys of EP2-/- as well as the EP4-/- vasodilatation at low PGE2 concentrations was prevented while the vasoconstriction at higher concentrations was augmented. In contrast, the vasodilatatory component was pronounced in kidneys of EP1 and EP3 knockout mice while in both genotypes the vasoconstriction at higher PGE2 concentrations was markedly blunted.
Our data provide evidence that PGE2 stimulates renin release via activation of EP2 and EP4 receptors, while EP1 and EP3 receptors appear to be without functional relevance in JGE cells. In contrast, all four receptor subtypes are involved in the control of renal vascular tone, EP1 and EP3 receptors increasing and EP2 as well as EP4 receptors decreasing it.
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