Alpha-adrenergic stimulation of prostaglandin release from rabbit iris-ciliary body in vitro.
Because previous studies have suggested that ocular effects of adrenergic agonists are in part attributable to arachidonate metabolites, the effect of phenylephrine on synthesis and release of arachidonic acid (AA) and prostaglandins from isolated rabbit iris-ciliary body (ICB) slices was examined. ICB concentrated and incorporated exogenous 14C-AA into tissue phospholipid and neutral lipid stores. During the period of 14C-AA labeling of tissue lipids, a portion of AA was converted to prostaglandins (PGs), as determined by thin-layer chromatography in two solvent systems and by prevention of PG synthesis by indomethacin. PGs E2 and F2 alpha were the major PGs synthesized. PGD2, thromboxane B2, and 6-keto-PGF 1 alpha were also synthesized by ICB. Phenylephrine enhanced PGE2 and PGF2 alpha synthesis and release from superfused 14C-AA-labeled ICB. PGE2 was the major PG released upon stimulation by phenylephrine. Phenoxybenzamine, an alpha-adrenergic receptor antagonists, and indomethacin prevented phenylephrine-induced PG release. The phenylephrine-induced PG release thus represented newly synthesized PG and was a result of the alpha-adrenergic activity of phenylephrine. Phenoxybenzamine treatment did not inhibit enzymes involved in PG synthesis, inasmuch as bradykinin was capable of markedly stimulating PG release from IBC treated with phenoxybenzamine. Esterification of 14C-AA into a lipid tentatively identified as 1,2-diacylglycerol was also demonstrated. The presence of this glyceride suggests that ICB exhibits phosphatidylinositol turnover and that phospholipase C and diacylglycerol lipase activities might be involved in supplying AA for ocular PG synthesis upon alpha-adrenergic stimulation.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007498:Iris / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D001095:Arachidonic Acids; D011453:Prostaglandins; D010643:Phenoxybenzamine; D010656:Phenylephrine; D016718:Arachidonic Acid; D007213:Indomethacin