Morphine-induced reduction of intraocular pressure and pupil diameter: Role of nitric oxide
Morphine-induced reduction of intraocular pressure and pupil diameter: Role of nitric oxide
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DOI：
10.1159/000091993
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发表时间：
2006-01-01
期刊：
影响因子：
3.1
通讯作者：
Russell, Karen R. M.
中科院分区：
文献类型：
--
作者：
Dortch-Carnes, Juanita;Russell, Karen R. M.
本研究旨在探讨一氧化氮在吗啡降眼压和缩瞳作用中的作用。使用经校准的气压计测量清醒、正常、暗适应的新西兰白色兔的IOP。进行实验，其中兔眼局部和单侧用吗啡处理，而对侧眼接受赋形剂。在吗啡给药前0.5和0 h以及给药后0.5、11、2、3、4和5 h测量眼压和瞳孔直径（PD）。还测定了非选择性阿片受体拮抗剂（纳洛酮）、一氧化氮合酶抑制剂（N ω-硝基-L-精氨酸甲酯; L-NAME）和巯基试剂（还原型L-谷胱甘肽; GSH）对吗啡介导的IOP和PD变化的影响。吗啡（10、33和100 μ g）在新西兰白色兔治疗和未治疗的眼睛中均产生浓度依赖性的IOP降低和PD降低。吗啡（100 μ g）的降IOP作用和PD的减少均被纳洛酮（100 μ g）、L-NAME（0.5%）或GSH（100 μ g）预处理显著抑制。本研究的结果表明，吗啡诱导的低眼压和PC减少是阿片受体介导的反应，与一氧化氮的释放有关。由于μ 3阿片受体亚型具有一氧化氮释放活性，并对GSH失活敏感，因此可以得出结论，吗啡诱导的低眼压和瞳孔缩小部分由μ 3阿片受体激活介导。版权所有（c）2006 S. Karger AG，巴塞尔。
The present study was performed to evaluate the role of nitric oxide in the intraocular pressure (IOP) lowering effect and in the miotic action of morphine. The IOP was measured in conscious, normal, dark-adapted New Zealand white rabbits using a calibrated pneumatonometer. Experiments were conducted, in which rabbits' eyes were treated with morphine topically and unilaterally, while the fellow eyes received vehicle. IOP and pupil diameter (PD) measurements were taken 0.5 and 0 h before morphine administration and 0.5,11, 2, 3, 4, and 5 h thereafter. The effects of a nonselective opioid receptor antagonist (naloxone), a nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME), and a sulfhydryl reagent (reduced L-glutathione; GSH) on morphine-mediated changes in IOP and PD were also determined. Morphine (10, 33, and 100 mu g) produced concentration-dependent decreases in IOP and reduced PD in both treated and untreated eyes of New Zealand white rabbits. IOP-lowering effect of morphine (100 mu g) and reduction in PD were both significantly inhibited by pretreatment with naloxone (100 mu g), L-NAME (0.5%), or GSH (100 mu g). The results from this study indicate that morphine-induced ocular hypotension and reduction in PC) are opioid-receptor-mediated responses that are associated with the release of nitric oxide. Because the mu 3 opioid receptor subtype has a nitric-oxide-releasing activity and is sensitive to inactivation by GSH, it is concluded that morphine-induced ocular hypotension and miosis are mediated, in part, by activation of mu 3 opioid receptors. Copyright (c) 2006 S. Karger AG, Basel.