Effect of in vivo administration of naloxone on ATP-ase's enzyme systems of synaptic plasma membranes from rat cerebral cortex.
Naloxone is a specific competitive antagonist of morphine, acting on opiate receptors, located on neuronal membranes. The effects of in vivo administration of naloxone on energy-consuming non-mitochondrial ATP-ases were studied in two different types of synaptic plasma membranes from rat cerebral cortex, known to contain a high density of opiate receptors. The enzyme activities of Na+, K(+)-ATP-ase, Ca(2+), Mg(2+)-ATP-ase and Mg(2+)-ATP-ase and of acetylcholinesterase (AChE) were evaluated on synaptic plasma membranes obtained from control and treated animals with effective dose of naloxone (12microg x kg(-1) i.m. 30 minutes). In control (vehicle-treated) animals specific enzyme activities assayed on these two types of synaptic plasma membranes are different, being higher on synaptic plasma membranes of II type than of I type, because the first fraction is more enriched in synaptic plasma membranes. The acute treatment with naloxone produced a significant decrease in Ca(2+),Mg(2+)-ATP-ase activity and an increase in AChE activity, only in synaptic plasma membranes of II type. The decrease of Ca(2+), Mg(2+)-ATP-ase enzymatic activity and the increased AChE activity are related to the interference of the drug on Ca(2+) homeostasis in synaptosoplasm, that leads to the activation of calcium-dependent processes, i.e. the extrusion of neurotransmitter. These findings give further evidence that pharmacodynamic characteristics of naloxone are also related to increase [Ca(2+)]i, interfering with enzyme systems (Ca(2+), Mg(2+)-ATP-ase) and that this drug increases acetylcholine catabolism in synaptic plasma membranes of cerebral cortex.
Gorini
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Department of Physiological-Pharmacological Cellular-Molecular Sciences, University of Pavia, Italy.
Rancati
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D'Angelo
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A
Devecchi
E
E
Villa
R F
RF
D000110:Acetylcholinesterase / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013570:Synaptic Membranes / Q000187:drug effects* / Q000201:enzymology
D009292:Narcotic Antagonists; D009270:Naloxone; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases