ADENYLYL-CYCLASE IN HUMAN AND BOVINE TRABECULAR MESHWORK

Purpose. To determine the basic characteristics and responses of adeny lyl cyclase in trabecular tissues. Because the second messenger cyclic adenosine monophosphate can lower intraocular pressure by increasing outflow facility, it is of interest to know which signalling pathways stimulating adenylyl cyclase are involved. Methods. Adenylyl cyclase a ctivity of bovine and human trabecular meshwork membrane fractions and of whole tissue homogenates (bovine) to forskolin, manganese, fluoroa luminate, isoproterenol, prostaglandins (PGE1, PGE2, PGF2alpha), and v asoactive intestinal peptide, were evaluated. Results. In bovine trabe cular meshwork particulate fractions, adenylyl cyclase was stimulated 3.3- and 2.6-fold over basal by 60 and 2 muM forskolin, respectively, 2.2-fold by fluoroaluminate, and 1.5-fold by PGE, and PGE2, whereas no or a very week response was obtained with PGF2alpha, isoproterenol, a nd vasoactive intestinal peptide. PGE1-induced stimulation was dose-de pendent and G-protein-dependent, which provides evidence for EP recept or-mediated activation. Whole tissue homogenates of bovine trabecular meshwork did not differ from the particulate fractions. In human trabe cular meshwork membrane fractions adenylyl cyclase stimulation was mor e pronounced, 12.4- and 5.5-fold by 60 and 2 muM forskolin, respective ly, 8.2-fold by fluoroaluminate, and 3-fold by PGE1 and PGE2. PGF2alph a had no effect. Significant stimulation was obtained with isoproteren ol (2.8-fold) and with vasoactive intestinal peptide (1.8-fold). Concl usions. Human and bovine trabecular meshwork can be stimulated at all known activation levels of adenylyl cyclase. The human adenylyl cyclas e system, especially receptor-coupled activity, is more sensitive than that of bovines. Beta-adrenoreceptor stimulation, PGE2, and vasoactiv e intestinal peptide may have a local physiologic function by activati ng adenylyl cyclase in human trabecular meshwork.