EP1 and EP4 receptors mediate prostaglandin E-2 actions in the microcirculation of rat kidney

Vasodilator prostaglandin PGE(2) protects the kidney from excessive vasocon striction during contraction of extracellular fluid volume and pathophysiol ogical states. However, it is not yet clear which of the four known E-prost anoid (EP) receptors is localized to resistance vessels and mediates net va sodilation. In the present study, we assessed the presence, signal transduc tion, and actions of EP receptor subtypes in preglomerular arterioles of Sp rague-Dawley rat kidneys. RNA encoding EP1, an EP1-variant, and EP4 recepto rs was identified by RT-PCR in freshly isolated preglomerular microvessels; cultured preglomerular vascular smooth muscle cells (VSMC) had EP1-variant and EP4 RNA but lacked EP1.EP2 and EP3 receptors were undetectable in both vascular preparations. In studies of cell signaling, stimulation of cAMP b y various receptor agonists is consistent with primary actions of PGE(2) on the EP4 receptor, with no inhibition of cAMP by EP1 receptors. Studies of cytosolic calcium concentration in cultured renal VSMC support an inhibitor y role of EP4 during ANG II stimulation. In vivo renal blood flow (RBF) stu dies indicate that the EP4 receptor is the primary receptor mediating susta ined renal vasodilation produced by PGE(2), whereas the EP1 receptor elicit s transient vasoconstriction. The EP1-variant receptor does not appear to p ossess any cAMP or cytosolic calcium signaling capable of affecting RBF. Co llectively, these studies demonstrate that the EP4 receptor is the major re ceptor in preglomerular VSMC. EP4 mediates PGE(2)-induced vasodilation in t he rat kidney and signals through G(s) proteins to stimulate cAMP and inhib it cytosolic calcium concentration.