IOVS Drug Metabolism and Disposition
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(Investigative Ophthalmology and Visual Science. 2002;43:2727-2731.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

Inhibition by Brimonidine of Forskolin-Induced Nitrite Production in Isolated Pig Ciliary Processes

Rong Liu, Renyi Wu, Josef Flammer and Ivan O. Haefliger

From the Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Switzerland.

PURPOSE. To investigate by which mechanism the ocular hypotensive drug brimonidine (selective {alpha}2-adrenoreceptor agonist) inhibits the production of nitrite induced by forskolin in isolated porcine ciliary processes.

METHODS. Nitrite (a nitric oxide metabolite) was measured by Griess reaction in the medium surrounding the ciliary processes, before and after exposure to different drugs. Tissues were exposed for 120 minutes to forskolin (0.1 µM; an adenylylcyclase activator) or 8-bromo-cAMP (10 µM; a cAMP analogue). Some experiments were conducted in the presence of brimonidine (0.01–10 µM), yohimbine (0.1–10 µM; {alpha}2-adrenoreceptor antagonist), prazosin (10 µM; {alpha}1-adrenoreceptor antagonist), nicergoline (10 µM; an {alpha}1-adrenoreceptor antagonist), propranolol (10 µM; a ß-adrenoreceptor antagonist or ß-blocker), and/or pertussis toxin (2 µg/mL; PTX, a Gi-protein inhibitor).

RESULTS. Nitrite production induced by forskolin (133% ± 6%), but not that induced by 8-bromo-cAMP (133% ± 6%), was inhibited in a concentration-dependent manner by brimonidine (10 µM: 103% ± 4%, P < 0.001; EC50: 0.05 µM). The inhibitory effect of brimonidine was prevented by PTX (119% ± 7%, P < 0.01) and, in a concentration-dependent manner, by yohimbine (10 µM: 134% ± 9%; P < 0.01), but not by prazosin, nicergoline, or propranolol.

CONCLUSIONS. Reduction of the formation of aqueous humor in the ciliary body’s epithelium (and thus an intraocular pressure decrease) after {alpha}2-adrenergic receptor stimulation by brimonidine is known to be associated with a Gi-protein-mediated inhibition of adenylylcyclase activity. The present study indicates that, through a similar {alpha}2-adrenoreceptor/Gi-protein pathway, brimonidine can also inhibit nitrite production after adenylylcyclase activation (forskolin-induced) in isolated porcine ciliary processes.




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R. Wu, K. Yao, J. Flammer, and I. O. Haefliger
Role of Anions in Nitric Oxide-Induced Short-Circuit Current Increase in Isolated Porcine Ciliary Processes
Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 3213 - 3222.
[Abstract] [Full Text] [PDF]


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