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Berlinde G. Dijkstra, Andrea Schneemann, Philip F. Hoyng; Flow after Prostaglandin E1 Is Mediated by Receptor-Coupled Adenylyl Cyclase in Human Anterior Segments. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2622-2626.
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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 mm Hg, while flow was
continuously monitored. After a stabilization period, 6 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 · 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 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
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