Flow after prostaglandin E-1 is mediated by receptor-coupled adenylyl cyclase in human anterior segments

PURPOSE. To assess the effect of prostaglandin (PG) F-2 alpha and PGE(1) on now through the trabecular meshwork in organ preserved human anterior segm ents. METHODS. Isolated human anterior segments were perfused under standard cond itions at a constant pressure of 10 mm Hg, while flow was continuously moni tored. After a stabilization period, 6 consecutive concentrations of PGs we re administered. cAMP levels were determined in the perfusate at baseline c onditions and at 10(-6) M PG. RESULTS. Perfusion with concentrations ranging from 10(-10) to 10(-5) M PGE , resulted in a dose-dependent increase in flow (P < 0.0001), reaching a pl ateau of a 26% increase at 10(-7) M. Perfusion with PGF(2 alpha) or placebo (Eagle's minimum essential medium) did not influence baseline flow. cAMP p roduced by human anterior segments increased from 4.8 +/- 0.6 pmol . 30 min (-1) per anterior segment at baseline to 19.2 +/- 4.8 pmol . 30 min(-1) per anterior segment after perfusion with 10(-6) M PGE(1) (P < 0.005). Perfusi on with 10(-6) M PGF(2 alpha) did not influence baseline cAMP production. P erfusion with 10(-5) M GDP-beta-S, an inhibitor of G protein, before and in combination with 10(-6) M PGE(1) completely inhibited the increase in flow and cAMP production as observed after PGE, alone. Perfusion with 10(-5) M GDP-beta-S alone did nor affect baseline cAMP production, CONCLUSIONS. In organ preserved perfused human anterior segments, flow and cAMP production in the perfusate are not mediated by receptor-coupled adeny lyl cyclase activity at baseline conditions. Perfusion with PGE(1) is sugge sted to increase flow through the trabecular meshwork by stimulation of pro stanoid EP2 receptor subtype, EP4 receptor subtype, or both, coupled to G(( s)) protein, inducing activation of the adenylyl cyclase catalytic unit. Th e results may indicate a physiological role for EP2 receptor subtype, EP4 r eceptor subtype, or both in the modulation of flow through the trabecular m eshwork after stimulation.