Ocular hypotensive effects of melatonin receptor agonists in the rabbit:: further evidence for an MT3 receptor
Ocular hypotensive effects of melatonin receptor agonists in the rabbit:: further evidence for an MT3 receptor
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DOI：
10.1038/sj.bjp.0705118
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发表时间：
2003-03-01
影响因子：
7.3
通讯作者：
Peral, A
中科院分区：
文献类型：
--
作者：
Pintor, J;Pel치ez, T;Peral, A
1 褪黑激素参与夜间和白天光周期内眼压的控制。我们研究了通过褪黑激素受体激动剂和拮抗剂调节新西兰白兔眼压的受体。2 褪黑激素及其类似物：2-苯丙氨酸-褪黑激素、6-氯-褪黑激素、2-1-褪黑激素、5-甲氧基羰基氨基-N-乙酰色胺 (5-MCA-NAT) 和 N-乙酰色胺均能降低眼压。这些化合物的剂量反应分析得出褪黑激素的 pD(2) 值为 9.3 +/- 0.24； 6-Cl-褪黑激素为 9.0 +/- 0.09； 2-1-褪黑激素为 9.0 +/- 0.84； 5-MCA-NAT 为 8.9 +/- 0.07； 2-Phe-褪黑素为 8.7 +/- 0.18，N-乙酰色胺为 9.4 +/- 0.30（全部 n = 8）。3 剂量为 0.5 nmol（10 μl）褪黑素和选择性褪黑素 MT(3) 激动剂 5-MCA-NAT 时，可引起眼压更大程度的降低（22.8 +/- 2.3% 和分别比其他化合物低 32.5 +/- 1.4%。4 褪黑素受体拮抗剂哌唑嗪、DH-97 和 4-P-PDOT 以剂量依赖性方式逆转 5-MCA-NAT 的作用，哌唑嗪的 pA(2) 值为 13.5 +/- 0.17，DH-97 为 10.6 +/- 0.16， 4-P-PDOT 为 9.4 +/- 0.20 (n = 8)。5 胆碱受体拮抗剂（六甲铵和阿托品）以及 α(2)- 和 β(2)- 肾上腺素受体拮抗剂（育亨宾和 ICI 118,551）部分逆转了褪黑激素和 5-MCA-NAT 产生的作用，表明胆碱能和去甲肾上腺素能系统可能参与其中褪黑激素激动剂介导的降血压作用。 α(1)-肾上腺素受体拮抗剂 Corynanthine 没有显着效果。6 MT(3) 激动剂 5-MCA-NAT 的强降血压作用表明，该化合物可能是治疗眼内压异常升高的病症的有效药物。
1 Melatonin is involved in the control of intraocular pressure during the night and day photoperiod. We have investigated the receptor that regulates intraocular pressure in New Zealand white rabbits by means of agonists and antagonists of melatonin receptors.2 Melatonin and its analogues: 2-Phe-melatonin, 6-Cl-melatonin, 2-1-melatonin, 5- methoxycarbo-nylamino-N-acetyltryptamine (5-MCA-NAT) and N-acetyltryptamine all produced a reduction in intraocular pressure. Dose-response analysis for these compounds gave pD(2) values of 9.3 +/- 0.24 for melatonin; 9.0 +/- 0.09 for 6-Cl-melatonin; 9.0 +/- 0.84 for 2-1-melatonin; 8.9 +/- 0.07 for 5-MCA-NAT; 8.7 +/- 0.18 for 2-Phe-melatonin and 9.4 +/- 0.30 for N-acetyltryptamine (all n = 8).3 At a dose of 0.5 nmol (in 10 mul) melatonin and the selective melatonin MT(3) agonist 5-MCA-NAT, induced greater reductions of intraocular pressure (22.8 +/- 2.3% and 32.5 +/- 1.4%, respectively) than the other compounds.4 The melatonin-receptor antagonists, prazosin, DH-97 and 4-P-PDOT, reversed the effect of 5-MCA-NAT in a dose-dependent manner, with pA(2) values of 13.5 +/- 0.17 for prazosin, 10.6 +/- 0.16 for DH-97 and 9.4 +/- 0.20 for 4-P-PDOT (n = 8).5 Cholinoceptor antagonists (hexamethonium and atropine) and alpha(2)- and beta(2)-adrenoceptor antagonists (yohimbine and ICI 118,551) partially reversed the effects produced by melatonin and 5-MCA-NAT, suggesting the possible involvement of cholinergic and noradrenergic systems in the hypotensive actions mediated by melatonin agonists. The alpha(1)-adrenoceptor antagonist, corynanthine, had no significant effect.6 The strong hypotensive effect of the MT(3) agonist, 5-MCA-NAT, suggests that this compound may be a useful agent for treating those pathologies where intraocular pressure is abnormally elevated.