Morphine-induced nitric oxide production in isolated, iris-ciliary bodies.
Considerable evidence suggests that the nitric oxide (NO)/cGMP signaling pathway plays an integral role in opioid receptor-mediated responses in the cardiovascular and immune systems. Previous studies in our laboratory and others have shown that nitric oxide (NO) plays a role in morphine-induced reduction of intraocular pressure (IOP) and pupil diameter (PD) in the New Zealand white (NZW) rabbit. The present study is designed to determine the effect of morphine on NO production in the isolated, iris-ciliary body (ICB), site of aqueous humor production, as this effect could be associated with morphine-stimulated changes in aqueous humor dynamics and iris function. ICBs obtained from normal NZW rabbits were utilized in these experiments. In some experiments, ICB samples were treated with morphine (1, 10 and 100 microM) for 1 h and later examined for changes in NO levels using a NO detection kit. In other experiments, tissue samples were pretreated with naloxone (non-selective opioid receptor antagonist), L-NAME (non-selective NO-synthase inhibitor) or GSH (sulfhydryl reagent) for 30 min, followed by treatment with morphine (10 muM). Morphine caused a concentration-dependent increase in the release of NO from ICBs. Levels of NO detected in the incubation medium of ICB samples increased from 1.49 +/- 0.19 (control) to 8.81 +/- 2.20 microM/mg protein (morphine-treated; 100 microM). Morphine-stimulated release of NO was significantly inhibited in tissues pretreated with 10 microM naloxone, L-NAME, or GSH. Results obtained from this study suggest that morphine stimulates NO release from the ICB through a mechanism that involves activation of NO-releasing opioid receptors. These results support the in vivo effects of morphine demonstrated in previous studies.
Dortch-Carnes
Juanita
J
Department of Pharmacology & Toxicology, Morehouse School of Medicine, 720 Westview Dr., Atlanta, GA, 30310-1495, USA. address: jcarnes@msm.edu
Randall
Karen Russell
KR
D000818:Animals; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009569:Nitric Oxide; D009270:Naloxone; D009020:Morphine; D019001:Nitric Oxide Synthase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester