The effects of forskolin on cyclic AMP, intraocular pressure and aqueous humor formation in rabbits.
Forskolin was used to study cyclic AMP-mediated regulation of aqueous humor dynamics in rabbits. Crystalline forskolin was solubilized in oil and its pharmacological effects were studied both in vitro and following topical ocular administration. In vitro, using cultured corneal epithelial cells, forskolin rapidly stimulated cyclic AMP production and in vivo increased cyclic AMP concentration in the aqueous humor 10-fold following topical administration. The effect of topical forskolin on intraocular pressure and aqueous humor formation was determined in vivo using pneumatonometry and fluorophotometry, respectively. Forskolin caused a prolonged reduction of intraocular pressure and decreased aqueous humor formation. The ability of forskolin to potentiate the ocular hypotensive effect of epinephrine was investigated. Forskolin in combination with epinephrine caused a decrease in intraocular pressure of longer duration than either 0.1% epinephrine or 1% forskolin administered separately. Forskolin caused a small but significant increase in the permeability of the blood-aqueous barrier at the time of maximal intraocular pressure reduction. This effect on the blood-aqueous barrier may explain the inhibitory effect of forskolin on aqueous humor formation.
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004338:Drug Combinations; D004837:Epinephrine / Q000494:pharmacology; D005123:Eye / Q000098:blood supply; D005470:Fluorometry; D066298:In Vitro Techniques; D007429:Intraocular Pressure / Q000187:drug effects*; D010783:Photometry; D011817:Rabbits
D004338:Drug Combinations; D005576:Colforsin; D000242:Cyclic AMP; D004837:Epinephrine