Adenylyl cyclase in human and bovine trabecular meshwork

Purpose. To determine the basic characteristics and responses of adenylyl 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 activity of bovine and human trabecular meshwork membrane fractions and of whole tissue homogenates (bovine) to forskolin, manganese, fluoroaluminate, isoproterenol, prostaglandins (PGE₁, PGE₂, PGF(2α)), and vasoactive intestinal peptide, were evaluated. Results. In bovine trabecular meshwork particulate fractions, adenylyl cyclase was stimulated 3.3- and 2.6-fold over basal by 60 and 2 μM forskolin, respectively, 2.2-fold by fluoroaluminate, and 1.5-fold by PGE₁ and PGE₂, whereas no or a very week response was obtained with PGF(2α), isoproterenol, and vasoactive intestinal peptide. PGE₁-induced stimulation was dose-dependent and G-protein-dependent, which provides evidence for EP receptor-mediated activation. Whole tissue homogenates of bovine trabecular meshwork did not differ from the particulate fractions. In human trabecular meshwork membrane fractions adenylyl cyclase stimulation was more pronounced, 12.4- and 5.5-fold by 60 and 2 μM forskolin, respectively, 8.2-fold by fluoroaluminate, and 3-fold by PGE₁ and PGE₂. PGF(2α) had no effect. Significant stimulation was obtained with isoproterenol (2.8-fold) and with vasoactive intestinal peptide (1.8-fold). Conclusions. Human and bovine trabecular meshwork can be stimulated at all known activation levels of adenylyl cyclase. The human adenylyl cyclase system, especially receptor- coupled activity, is more sensitive than that of bovines. Beta- adrenoreceptor stimulation, PGE₂, and vasoactive intestinal peptide may have a local physiologic function by activating adenylyl cyclase in human trabecular meshwork.