Regulation of aqueous flow by the adenylate cyclase receptor complex in the ciliary epithelium.
The answer to how the beta-adrenergic receptor mediates a fall in intraocular pressure has been elusive. Methods of measurement have not been refined sufficiently. The separate changes after adrenergic treatment frequently are small, and the tissue effects are multiple. On a molecular basis, stimulation of the beta-adrenergic receptor activates intracellular adenylate cyclase to produce increased cyclic adenosine monophosphate. Acting by different cell-receptor mechanisms, but nonetheless potent, nonadrenergic stimulators of adenylate cyclase in the ciliary epithelium, such as cholera toxin and organic fluorides, have been studied in experimental animals. They reduce intraocular pressure by reducing net aqueous flow. When forskolin, a diterpene and potent stimulator of adenylate cyclase, became available, it was used in noninvasive topical form in the human eye to clarify the question of whether increased cyclic adenosine monophosphate reduces intraocular pressure and aqueous flow. Noninvasive studies in human eyes have demonstrated a 35% reduction in outflow pressure after the administration of forskolin in a 1% topical suspension, matched by a corresponding reduction in aqueous flow. Tonographic outflow facility was unaltered. Thus, the entire reduction in intraocular pressure can be accounted for by a reduction in net aqueous flow.
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D020727:ADP-Ribosylation Factors; D000262:Adenylyl Cyclases / Q000502:physiology; D000328:Adult; D000368:Aged; D000867:Anterior Chamber / Q000378:metabolism; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability; D002924:Ciliary Body / Q000378:metabolism*; D005576:Colforsin; D000242:Cyclic AMP / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008565:Membrane Proteins / Q000502:physiology*; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013999:Timolol / Q000494:pharmacology
D004224:Diterpenes; D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D013999:Timolol; D000242:Cyclic AMP; D020727:ADP-Ribosylation Factors; D000262:Adenylyl Cyclases