The aim of this study was to investigate the hypotensive effect of the melatonin analogue, N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethanamine (IIK7), through MT(2)-melatonin receptors and the involvement of the sympathetic nervous system in this action in New Zealand rabbit eyes. The topical application of melatonin or IIK7 produced a reduction in intraocular pressure of 20.2 +/- 5.3% and 38.5 +/- 3.2% respectively. This effect was concentration-dependent; it was blocked by selective MT(2) receptor antagonists and was severely diminished after chemical sympathectomy. Immunohistochemistry and western blot analysis showed the ciliary processes as the site of this action and no co-localization of MT(2)-melatonin receptor with the sympathetic nervous system was observed. The beta-adrenergic agonists, terbutaline and salbutamol, potentiated the hypotensive effect of IIK7 reducing intraocular pressure (IOP) 41.75 +/- 4.26% and 44.7 +/- 5.6% respectively. Also, IIK7 in presence of the nonspecific protein phosphatase inhibitor okadaic acid, lowered IOP 32.2 +/- 4.5% and in presence of forskolin plus 3-isobutyl-1-methylxanthine decreased IOP in 32.2 +/- 5.47%. These data suggest that the melatonin agonist IIK7 reduces intraocular pressure by acting through MT(2)-melatonin receptors presumably decreasing aqueous humour formation. Also, in the presence of beta-adrenoceptor agonists MT(2)-melatonin receptors activity increase their ability to reduce IOP.

中文翻译：

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交感神经系统调节血压正常兔的MT2-褪黑激素受体的眼压降低作用。

这项研究的目的是通过MT研究褪黑激素类似物N-丁酰基-2-（2-甲氧基-6H-异吲哚并[2,1-a]吲哚-11-基）乙胺（IIK7）的降压作用（2）褪黑激素受体和交感神经系统在新西兰兔眼中的这种作用。褪黑激素或IIK7的局部应用可使眼内压分别降低20.2 +/- 5.3％和38.5 +/- 3.2％。这种作用是浓度依赖性的。它被选择性的MT（2）受体拮抗剂阻断，并在化学交感神经切除术后严重减轻。免疫组织化学和蛋白质印迹分析显示该过程的位置的纤毛过程，并没有观察到MT（2）褪黑素受体与交感神经系统的共定位。β-肾上腺素能激动剂特布他林和沙丁胺醇，增强了IIK7的降压作用，分别降低了41.75 +/- 4.26％和44.7 +/- 5.6％的眼内压（IOP）。同样，在非特异性蛋白磷酸酶抑制剂冈田酸存在下，IIK7使IOP降低32.2 +/- 4.5％，在福司可林加3-异丁基-1-甲基黄嘌呤的存在下使IOP降低32.2 +/- 5.47％。这些数据表明，褪黑激素激动剂IIK7通过通过MT（2）-褪黑素受体起作用，降低眼内压，可能减少房水的形成。此外，在β-肾上腺素受体激动剂的存在下，MT（2）-褪黑激素受体活性增加了它们降低IOP的能力。5％和福司可林加3-异丁基-1-甲基黄嘌呤的存在使IOP降低32.2 +/- 5.47％。这些数据表明，褪黑激素激动剂IIK7通过通过MT（2）-褪黑激素受体起作用，降低眼内压，可能减少房水的形成。此外，在β-肾上腺素受体激动剂的存在下，MT（2）-褪黑激素受体活性增加了它们降低IOP的能力。5％和福司可林加3-异丁基-1-甲基黄嘌呤的存在使IOP降低32.2 +/- 5.47％。这些数据表明，褪黑激素激动剂IIK7通过通过MT（2）-褪黑激素受体起作用，降低眼内压，可能减少房水的形成。此外，在β-肾上腺素受体激动剂的存在下，MT（2）-褪黑激素受体活性增加了它们降低IOP的能力。