Proteinase-activated receptors 1-4 (PAR1-4) are highly expressed in the kidney and are thought to regulate renal hemodynamics. Moreover, the proteinase thrombin that, besides its central role in the coagulation cascade, activates PARs has been reported to decrease plasma renin activity in rats. In order to test for the relative impact of the respective PARs on renin release the effects of PAR1-, PAR2- and PAR4-activating peptides (TFLLR, SLIGRL and AYPGKF respectively) on renin secretion rates (RSR) from isolated perfused mouse kidneys were investigated. Both thrombin and TFLLR dose-dependently suppressed RSR and reduced perfusate flow in kidneys prestimulated with the ß-adrenoreceptor agonist isoproterenol. While TFLLR nearly abolished the stimulations of RSR in response to the loop diuretic bumetanide, to prostaglandin E₂ or to a decrease in renal perfusion pressure, it did not suppress RSR in the absence of extracellular calcium, suggesting a calcium-dependent inhibition of renin release by PAR-1. The PAR2-activating peptide SLIGRL concentration-dependently increased RSR and perfusate flow in the absence and the presence of isoproterenol. The stimulation of RSR by SLIGRL was markedly attenuated by L-NAME, suggesting a nitric-oxide-dependent mechanism. Activation of PAR4 by AYPGKF did not modulate RSR or perfusate flow. PAR1 and PAR2 immunoreactivity were detected in the juxtaglomerular region and were co-localized with renin immunoreactivity. Our data provide evidence that PAR1 activation inhibits renal renin secretion and induces renal vasoconstriction via a calcium-dependent mechanism, whereas PAR2 activation stimulates renin release and induces vasodilation mainly via the release of nitric oxide.