REGULATION OF RENAL-FUNCTION BY PROSTAGLANDIN-E RECEPTORS

Prostaglandin E-2 is the major cyclooxygenase product of arachidonic a cid metabolism produced along the nephron. This autacoid interacts wit h four distinct, G-protein-coupled E-prostanoid receptors designated E P1-EP4. The intrarenal distribution of each receptor has been mapped a nd the consequences of receptor activation examined. EP3 receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP3 receptor activation inhibits cAMP generation via G(i), thus inhibiting vasopressin-stimulated water reabsorption i n the CD. EP3 receptor activation also may contribute to PGE(2)-mediat ed inhibition of NaCl absorption in the mTAL. The EP1 receptor is coup led to increased cell [Ca2+]. EP1 mRNA expression is restricted to the CD, and receptor activation inhibits Na+ absorption. PGE(2) also incr eases cAMP generation in the cortical thick ascending limb and CD; thi s may be due to EP4 receptor activation. EP4 mRNA is readily detected in the CD with little detectable EP2 expression. The EP4 receptor appe ars to be expressed both on luminal and basolateral membranes. EP4 rec eptor activation also may contribute to the regulation of renin releas e by the juxtaglomerular apparatus. The consequences of renal EP-recep tor activation for salt and water balance may be determined by the rel ative renal expression of each of these receptors.