Timolol inhibits adenylate cyclase activity in the iris-ciliary body and trabecular meshwork of the eye and blocks activation of the enzyme by salbutamol.
The enzymatic activity of adenylate cyclase in homogenates and membrane-rich fractions prepared from rabbit iris-ciliary bodies and bovine trabecular meshwork was found to be inhibited by timolol. Treatment of iris-ciliary body homogenates with Triton X-305 resulted in abolition of the inhibitory effect of the drug on the activity of the enzyme. The stimulatory effect of salbutamol on the enzyme was also susceptible to blockade by timolol. It is suggested that the hypotensive action of timolol on intraocular pressure results from structural and functional changes induced on the plasma membranes of the iris-ciliary body and trabecular meshwork by the thiadiazole group of the molecule, and, also, from the occupation of the adrenergic receptors of the iris-ciliary body by the tert-butylamino-2-hydroxypropoxy part of the compound.
D000255:Adenosine Triphosphate / Q000032:analysis; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002924:Ciliary Body / Q000187:drug effects / Q000201:enzymology*; D000242:Cyclic AMP / Q000302:isolation & purification; D004789:Enzyme Activation / Q000187:drug effects; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D013999:Timolol / Q000494:pharmacology*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000201:enzymology*
D011092:Polyethylene Glycols; D013999:Timolol; D000255:Adenosine Triphosphate; D017830:Octoxynol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000420:Albuterol