title: Inhibition by brimonidine of forskolin-induced nitrite production in isolated pig ciliary processes.
abstract: OBJECTIVE
  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 microM; an adenylylcyclase activator) or 8-bromo-cAMP (10 microM; a cAMP analogue). Some experiments were conducted in the presence of brimonidine (0.01-10 microM), yohimbine (0.1-10 microM; alpha(2)-adrenoreceptor antagonist), prazosin (10 microM; alpha(1)-adrenoreceptor antagonist), nicergoline (10 microM; an alpha(1)-adrenoreceptor antagonist), propranolol (10 microM; a beta-adrenoreceptor antagonist or beta-blocker), and/or pertussis toxin (2 microg/mL; PTX, a G(i)-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 microM: 103% +/- 4%, P < 0.001; EC(50): 0.05 microM). The inhibitory effect of brimonidine was prevented by PTX (119% +/- 7%, P < 0.01) and, in a concentration-dependent manner, by yohimbine (10 microM: 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 G(i)-protein-mediated inhibition of adenylylcyclase activity. The present study indicates that, through a similar alpha(2)-adrenoreceptor/G(i)-protein pathway, brimonidine can also inhibit nitrite production after adenylylcyclase activation (forskolin-induced) in isolated porcine ciliary processes.
authors.affiliation: Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Switzerland.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Renyi
authors.initials: R
authors.lastname: Wu
authors.forename: Josef
authors.initials: J
authors.lastname: Flammer
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Haefliger
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D037342:Pertussis Toxin; D011810:Quinoxalines / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013552:Swine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D009573:Nitrites; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000068438:Brimonidine Tartrate; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases