Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Catania, Italy.
J Ocul Pharmacol Ther. 2010 Feb;26(1):31-5. doi: 10.1089/jop.2009.0081.
Recent findings generated from our laboratory have demonstrated the involvement of nitric oxide (NO) in morphine-induced reduction of intraocular pressure (IOP). The present study was designed to investigate the possible involvement of carbon monoxide (CO) in morphine-induced reduction of IOP and the role of mu(3) opioid receptors.
New Zealand rabbits were used in this study. They were pretreated with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 1%, 30 microL), or an inhibitor of heme oxygenase (HO), zinc protoporphyrin-IX (ZnPP-IX; 0.1 mg/kg; i.v.). The same animals were then treated with morphine (100 microg/30 microL) with or without NO or CO donors administration, sodium nitroprusside (SNP) and tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), respectively. A separate set of animals were pretreated with the nonselective opioid receptor antagonist, naloxone (100 microg/30 microL), or the micro(3) opioid receptor inhibitor, L-glutathione (GSH, 1%, 30 microL), in the presence of SNP or CORM-3 followed by morphine administration. IOP measurements were taken at different times after monolateral instillation of morphine.
Morphine induced a significant decrease in IOP and pretreatment with ZnPP-IX or L-NAME significantly prevented this effect whereas administration of NO or CO donors amplified morphine-induced decrease in IOP. This effect was partially abrogated both by pretreatment with ZnPP-IX or L-NAME, and by pretreatment with naloxone and GSH suggesting that the decrease in IOP relies on exogenous NO and CO liberated from SNP and CORM-3, respectively.
We conclude that the endogenous NO/CO system and micro(3) receptors contribute to morphine-induced ocular hypotension and that the reduction of IOP elicited by morphine can be augmented by exogenous NO and CO.
我们实验室的最新研究结果表明，一氧化氮（NO）参与了吗啡引起的眼压（IOP）降低。本研究旨在探讨一氧化碳（CO）是否参与吗啡引起的IOP 降低，以及μ3 阿片受体的作用。
本研究使用新西兰兔。它们先用一氧化氮合酶抑制剂 Nω-硝基-L-精氨酸甲酯（L-NAME，1%，30μL）或血红素加氧酶抑制剂锌原卟啉-IX（ZnPP-IX；0.1mg/kg；静脉注射）预处理。然后，同一批动物给予吗啡（100μg/30μL），同时给予或不给予一氧化氮或一氧化碳供体，分别为硝普钠（SNP）和三羰基氯（甘氨酸）钌（II）（CORM-3）。另一组动物先用非选择性阿片受体拮抗剂纳洛酮（100μg/30μL）或μ3 阿片受体抑制剂 L-谷胱甘肽（GSH，1%，30μL）预处理，然后给予 SNP 或 CORM-3 后再给予吗啡。在单侧滴注吗啡后不同时间测量眼压。
吗啡引起眼压显著降低，ZnPP-IX 或 L-NAME 预处理显著阻止了这种作用，而给予一氧化氮或一氧化碳供体则放大了吗啡引起的眼压降低。这种作用部分被 ZnPP-IX 或 L-NAME 的预处理以及纳洛酮和 GSH 的预处理所阻断，这表明眼压的降低依赖于 SNP 和 CORM-3 分别释放的外源性一氧化氮和一氧化碳。
我们得出结论，内源性 NO/CO 系统和 μ3 受体参与了吗啡引起的眼压低，吗啡引起的眼压降低可以通过外源性一氧化氮和一氧化碳来增强。
