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Abstract #15519 Published in IGR 1-3
Flow after prostaglandin E1 is mediated by receptor-coupled adenylyl cyclase in human anterior segments
Dijkstra BG; Schneemann A; Hoyng PFInvestigative Ophthalmology and Visual Science 1999; 40: 2622-2626
PURPOSE: To assess the effect of prostaglandin (PG) F2α and PGE1 on flow through the trabecular meshwork in organ preserved human anterior segments. METHODS: Isolated human anterior segments were perfused under standard conditions at a constant pressure of 10 mmHg, while flow was continuously monitored. After a stabilization period, six consecutive concentrations of PGs were administered. cAMP levels were determined in the perfusate at baseline conditions and at 10-6 M PG. RESULTS: Perfusion with concentrations ranging from 10-10 to 10-5 M PGE1 resulted in a dose-dependent increase in flow (p < 0.0001), reaching a plateau of a 26% increase at 10-7 M. Perfusion with PGF2α or placebo (Eagle's minimum essential medium) did not influence baseline flow. cAMP produced by human anterior segments increased from 4.8±0.6 pmol x 30 min-1 per anterior segment at baseline to 19.2±4.8 pmol x 30 min-1 per anterior segment after perfusion with 10-6 M PGE1 (p < 0.005). Perfusion with 10-6 M PGF2α did not influence baseline cAMP production. Perfusion with 10-5 M GDP-β-S, an inhibitor of G protein, before and in combination with 10-6 M PGE1 completely inhibited the increase in flow and cAMP production as observed after PGE1 alone. Perfusion with 10-5 M GDP-β-S alone did not 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 adenylyl cyclase activity at baseline conditions. Perfusion with PGE1 is suggested to increase flow through the trabecular meshwork by stimulation of prostanoid EP2 receptor subtype, EP4 receptor subtype, or both, coupled to G(s) protein, inducing activation of the adenylyl cyclase catalytic unit. The results may indicate a physiological role for EP2 receptor subtype, EP4 receptor subtype, or both in the modulation of flow through the trabecular meshwork after stimulation.
Dr. B.G. Dijkstra, The Netherlands Ophthalmic Research Institute, Amsterdam; The Netherlands
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
