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J. Carnes, D.E. Potter; Delta Opioid Agonist-Stimulated Inositol Phosphate Production and Inhibition of cAMP Accumulation: Role of Gi/o Protein Beta Gamma Subunits 0 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4389.
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Purpose: Our laboratory has previously demonstrated the ability of opioid agonists to decrease intraocular pressure (IOP) of rabbits, and inhibit forskolin (Forsk)-stimulated cAMP production, as well as increase the production of inositol phosphate (IP) in isolated iris-ciliary bodies (ICB). The present study is designed to evaluate the role of Gi/o protein beta gamma subunits in delta opioid agonist-mediated changes in cAMP and IP production in the isolated, rabbit ICB. Methods: Changes in Forsk-stimulated cAMP accumulation were measured using enzyme immunoassay after the following treatments: (1) 1 hr incubation of tissue segments with the delta opioid receptor agonist, SNC-80 (10-12 to 10-7 M), (2) 30 min pretreatment with the delta opioid receptor antagonist, naltrindole (1 µM) followed by additon of SNC-80 (3) pretreatment with pertussis toxin (PTX) followed by addition of SNC-80 and (4) pretreatment (1 hr) of tissue segments with the G beta gamma subunit scavenger, phosducin (1 nM), followed by addition of SNC-80. IP production was measured by ion exchange chromatography following the same treatment regimens for cAMP. Results: The highly selective delta receptor agonist, SNC-80, produced concentration-dependent increases in the levels of IP1 as well as inhibited Forsk-stimulated cAMP produciton in a concentration-dependent manner. The SNC-80-induced increase in IP1 levels was diminished in the presence of naltrindole. In addition, pretreatment of tissue samples with phosducin abated the effect of SNC-80 on both cAMP and IP production. Conclusions: Results from this study indicate that the delta opioid receptor-mediated increases in IP production and inhibition of Forsk-stimulated cAMP formation are PTX-sensitive responses that involve the release of G beta gamma subunits. Thus, this activity could be involved in delta opioid agonist-induced reduction of IOP in rabbits.
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