EP(1) and EP(4) receptors mediate prostaglandin E(2) actions in the microcirculation of rat kidney.
Vasodilator prostaglandin PGE(2) protects the kidney from excessive vasoconstriction during contraction of extracellular fluid volume and pathophysiological states. However, it is not yet clear which of the four known E-prostanoid (EP) receptors is localized to resistance vessels and mediates net vasodilation. In the present study, we assessed the presence, signal transduction, and actions of EP receptor subtypes in preglomerular arterioles of Sprague-Dawley rat kidneys. RNA encoding EP(1), an EP(1)-variant, and EP(4) receptors was identified by RT-PCR in freshly isolated preglomerular microvessels; cultured preglomerular vascular smooth muscle cells (VSMC) had EP(1)-variant and EP(4) RNA but lacked EP(1). EP(2) and EP(3) receptors were undetectable in both vascular preparations. In studies of cell signaling, stimulation of cAMP by various receptor agonists is consistent with primary actions of PGE(2) on the EP(4) receptor, with no inhibition of cAMP by EP(1) receptors. Studies of cytosolic calcium concentration in cultured renal VSMC support an inhibitory role of EP(4) during ANG II stimulation. In vivo renal blood flow (RBF) studies indicate that the EP(4) receptor is the primary receptor mediating sustained renal vasodilation produced by PGE(2), whereas the EP(1) receptor elicits transient vasoconstriction. The EP(1)-variant receptor does not appear to possess any cAMP or cytosolic calcium signaling capable of affecting RBF. Collectively, these studies demonstrate that the EP(4) receptor is the major receptor in preglomerular VSMC. EP(4) mediates PGE(2)-induced vasodilation in the rat kidney and signals through G(s) proteins to stimulate cAMP and inhibit cytosolic calcium concentration.
Purdy
K E
KE
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA.
Arendshorst
W J
WJ
D000818:Animals; D001160:Arterioles / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D003600:Cytosol / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology
C545637:Ptger1 protein, rat; C545652:Ptger4 protein, rat; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D015232:Dinoprostone; D002118:Calcium