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Abstract #15054 Published in IGR 8-4
Morphine-induced reduction of intraocular pressure and pupil diameter: role of nitric oxide
Dortch Carnes J; Russell KRPharmacology 2006; 77: 17-24
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, 1, 2, 3, 4, and 5 h thereafter. The effects of a nonselective opioid receptor antagonist (naloxone), a nitric oxide synthase inhibitor (Nomega-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 μg) 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 μg) and reduction in PD were both significantly inhibited by pretreatment with naloxone (100 μg), L-NAME (0.5%), or GSH (100 μg). The results from this study indicate that morphine-induced ocular hypotension and reduction in PD are opioid-receptor-mediated responses that are associated with the release of nitric oxide. Because the μ3 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 μ3 opioid receptors.
Dr. J. Dortch Carnes, Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA. jcarnes@msm.edu
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
6.1 Intraocular pressure measurement; factors affecting IOP (Part of: 6 Clinical examination methods)
5 Experimental glaucoma; animal models
