Biochemical evidence for PGI2 and PGE2 receptors in the rabbit renal preglomerular microvasculature.
It has been proposed that a portion of the biologic actions of vasodilator prostaglandins occurs via an interaction with specific adenylate cyclase-linked receptors. This hypothesis was explored further in the renal microvasculature by examining the effects of PGI2, PGE1, and PGE2 on rabbit preglomerular microvascular adenylate cyclase. A membrane preparation derived from freshly isolated rabbit renal preglomerular microvessels was used in these studies. NaF, forskolin, or 5'-guanylyl imidodiphosphate were found to be effective in increasing adenylate cyclase activity in the absence of exogenous guanosine-5'-triphosphate. A dose-dependent stimulation of adenylate cyclase was also observed with guanosine-5'-triphosphate. PGE1, PGE2, and PGI2 produced a dose-dependent stimulation of adenylate cyclase activity only in the presence of guanosine-5'-triphosphate suggesting that this nucleotide is essential for prostaglandin-induced stimulation of the enzyme. PGI2 exhibited a time-dependent increase in adenylate cyclase activity and this increased activity reached a plateau at 20-25 min. When PGE1 and PGE2 were added together, no additive effect on adenylate cyclase stimulation was noted whereas PGI2 and PGE2 when added together produced an additive stimulatory effect. When viewed together, these data suggest the presence of separate PGI2 and PGE adenylate cyclase-linked receptors in rabbit renal preglomerular microvessels. These findings also suggest that in the renal microvasculature, cyclic AMP may be a second messenger mediating the vasodilatory effects of both PGI2 and PGE2.
Chaudhari
A
A
Department of Medicine, University of California, Irvine.
Gupta
S
S
Kirschenbaum
M A
MA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects; D008833:Microcirculation / Q000378:metabolism; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D018078:Receptors, Prostaglandin E; D014665:Vasodilator Agents / Q000494:pharmacology*
D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D014665:Vasodilator Agents; D006160:Guanosine Triphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone