Dortch-Carnes Juanita, Russell Karen
Department of pharmacology/Toxicology Morehouse School of Medicine, 720 Westview Drive, SW Atlanta, GA 30310-1495, USA.
Exp Eye Res. 2007 Jan;84(1):185-90. doi: 10.1016/j.exer.2006.09.014. Epub 2006 Nov 13.
Recent studies in our laboratory have demonstrated a role of nitric oxide (NO) in morphine-induced reduction of intraocular pressure (IOP) and pupil diameter (PD) in the New Zealand white (NZW) rabbit. The present study was designed to determine the effect of morphine on NO release in the aqueous humor of NZW rabbits, as this effect could be associated with morphine-mediated changes in aqueous humor dynamics and iris function. Dark-adapted NZW rabbits were treated as follows: (1) treatment with morphine (10, 33 or 100 microg, 5 min); (2) treatment with morphine or endomorphin-1 for 5, 15 or 30 min; (3) pretreatment with naloxone (100 microg), L-NAME (125 microg) or reduced glutathione (GSH, 100 microg) for 30 min, followed by treatment with morphine (100 microg, 5 min). After the various treatment regimens, aqueous humor samples were obtained by paracenthesis and immediately assayed for nitrates and nitrites (an index of NO production), using a microplate assay kit. Morphine caused a dose-dependent increase in the levels of NO in aqueous humor after 5 min of treatment with each dose. Rabbits treated with endomorphin-1 (100 microg) had no significant change in NO levels in aqueous at any point in the course of time. Aqueous samples from rabbits treated with morphine (100 microg) for 5 min increased from 29.84+/-2.39 microM (control) to 183.94+/-23.48 microM (treated). The increase in NO levels by morphine (100 microg, 5 min) was completely inhibited in the presence of naloxone (100 microg), L-NAME (125 microg) or GSH (100 microg). These results indicate that morphine-induced increase in NO production in aqueous humor is a transient response that is linked to the activation of mu opioid receptors. Data obtained suggest that morphine-stimulated changes in ocular hydrodynamics and iris function are due, in part, to increased release of NO in aqueous humor. In addition, the sensitivity of the response to l-NAME and GSH suggests that morphine-induced release of nitric oxide into aqueous humor is mediated by activation of mu-3 opioid receptors found in the anterior segment of the eye.
我们实验室最近的研究表明，一氧化氮（NO）在新西兰白兔吗啡诱导的眼压（IOP）降低和瞳孔直径（PD）缩小中发挥作用。本研究旨在确定吗啡对新西兰白兔房水中NO释放的影响，因为这种影响可能与吗啡介导的房水动力学和虹膜功能变化有关。将暗适应的新西兰白兔按以下方式处理：（1）用吗啡（10、33或100微克，5分钟）处理；（2）用吗啡或内吗啡肽-1处理5、15或30分钟；（3）先用纳洛酮（100微克）、L- NAME（125微克）或还原型谷胱甘肽（GSH，100微克）预处理30分钟，然后用吗啡（100微克，5分钟）处理。在各种处理方案后，通过前房穿刺获取房水样本，并立即使用微孔板检测试剂盒检测硝酸盐和亚硝酸盐（NO产生的指标）。用每种剂量的吗啡处理5分钟后，吗啡导致房水中NO水平呈剂量依赖性增加。用内吗啡肽-1（100微克）处理的兔子在整个时间段内房水中NO水平无显著变化。用吗啡（100微克）处理5分钟的兔子的房水样本从29.84±2.39微摩尔（对照）增加到183.94±23.48微摩尔（处理后）。在存在纳洛酮（100微克）、L- NAME（125微克）或GSH（100微克）的情况下，吗啡（100微克，5分钟）引起的NO水平升高被完全抑制。这些结果表明，吗啡诱导的房水中NO产生增加是一种短暂反应，与μ阿片受体的激活有关。获得的数据表明，吗啡刺激的眼内流体动力学和虹膜功能变化部分归因于房水中NO释放增加。此外，对L- NAME和GSH反应的敏感性表明，吗啡诱导的一氧化氮释放到房水中是由眼前段发现的μ-3阿片受体激活介导的。
