Liu Rong, Wu Renyi, Flammer Josef, Haefliger Ivan O
Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Switzerland.
Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2727-31.
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.
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).
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.
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.
研究眼降压药物溴莫尼定（一种选择性α₂肾上腺素能受体激动剂）通过何种机制抑制离体猪睫状体中福斯高林诱导的亚硝酸盐生成。
在暴露于不同药物前后，通过格里斯反应测定睫状体周围培养基中的亚硝酸盐（一种一氧化氮代谢产物）。组织暴露于福斯高林（0.1微摩尔/升；一种腺苷酸环化酶激活剂）或8-溴-cAMP（10微摩尔/升；一种cAMP类似物）120分钟。一些实验在溴莫尼定（0.01 - 10微摩尔/升）、育亨宾（0.1 - 10微摩尔/升；α₂肾上腺素能受体拮抗剂）、哌唑嗪（10微摩尔/升；α₁肾上腺素能受体拮抗剂）、尼麦角林（10微摩尔/升；一种α₁肾上腺素能受体拮抗剂）、普萘洛尔（10微摩尔/升；一种β肾上腺素能受体拮抗剂或β阻滞剂）和/或百日咳毒素（2微克/毫升；PTX，一种G(i)蛋白抑制剂）存在的情况下进行。
福斯高林诱导的亚硝酸盐生成（133% ± 6%），而非8-溴-cAMP诱导的亚硝酸盐生成（133% ± 6%），被溴莫尼定以浓度依赖性方式抑制（10微摩尔/升：103% ± 4%，P < 0.001；半数有效浓度：0.05微摩尔/升）。溴莫尼定的抑制作用被PTX（119% ± 7%，P < 0.01）以及以浓度依赖性方式被育亨宾（10微摩尔/升：134% ± 9%；P < 0.01）所阻断，但未被哌唑嗪、尼麦角林或普萘洛尔阻断。
已知溴莫尼定刺激α₂肾上腺素能受体后睫状体上皮房水生成减少（从而眼压降低）与G(i)蛋白介导的腺苷酸环化酶活性抑制有关。本研究表明，通过类似的α₂肾上腺素能受体/G(i)蛋白途径，溴莫尼定在离体猪睫状体中腺苷酸环化酶激活（福斯高林诱导）后也能抑制亚硝酸盐生成。
