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• W2041226316 abstract "Morphine through μ-opioid receptors and Gi/o proteins modulates several cellular effector systems; however, the mechanisms involved in the regulation of Na+,K+-ATPase are not well known. We evaluated the effect of two μ-opioid receptor agonists on ouabain-sensitive Na+,K+-ATPase activity in mice forebrain synaptosomes, and examined the modulation of this effect by antagonists of opioid receptors and a blocker of Gi/o proteins. Incubation of synaptosomes with morphine (10−9 to 10−4 M) or buprenorphine (10−10 to 10−5 M) concentration-dependently stimulated Na+,K+-ATPase activity, morphine being less potent but more efficacious than buprenorphine. Morphine did not displace [3H]ouabain from its binding site (Na+,K+-ATPase) to forebrain membranes, whereas ouabain did so in a concentration-dependent manner. Naloxone, an opioid antagonist (10−6 M), added to the synaptosomal medium, antagonized the enhancement of Na+,K+-ATPase activity induced by morphine, producing a parallel shift to the right of the morphine concentration–response curve. Treatment with β-funaltrexamine, a μ antagonist (2.5 and 10 μg/mouse, i.c.v.) and naloxonazine, a μ1 antagonist (35 mg/kg, s.c.), 24 h before the synaptosomes were obtained, produced a dose-dependent reduction in the Emax of the morphine-induced increase in Na+,K+-ATPase activity in vitro, but did not significantly modify its EC50. Pertussis toxin (Gi/o protein blocker) treatment at a dose of 0.5 μg/mouse, administered i.c.v. 5 days before the synaptosomes were obtained, completely abolished the enhancement of Na+,K+-ATPase activity induced by morphine. A lower dose (0.25 μg/mouse) decreased the Emax of morphine by 50% but did not significantly affect its EC50. These results suggest that morphine indirectly enhances Na+,K+-ATPase activity in the brain by activating μ-opioid receptors and Gi/o proteins." @default.
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• W2041226316 date "2002-12-01" @default.
• W2041226316 modified "2023-09-27" @default.
• W2041226316 title "Mechanisms involved in morphine-induced activation of synaptosomal Na+,K+-ATPase" @default.
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• W2041226316 doi "https://doi.org/10.1016/s0006-8993(02)03663-6" @default.
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