Is intracellular sodium involved in the mechanism of tolerance to opioid drugs?
Recent studies indicate that one of the more likely mechanisms of opioid tolerance could involve a decrease in the efficiency with which agonists can induce coupling of their specific binding sites in neuronal membranes to the activation (or deactivation) of an effector system. Reports of sodium-induced decreases in opioid receptor agonist binding and in the size of ligand/receptor complexes, as well as modulation of opioid activity by manipulation of sodium in vivo, indicate that sodium might play a physiological role in modulating opioid receptor function. Reports of morphine-induced systemic sodium retention in animals, as well as morphine-induced increases in brain intracellular sodium and decreases in brain Na+, K(+)-ATPase activity, indicate that the development of tolerance may be accompanied by changes in the disposition of sodium. The direction of these sodium- and morphine-induced changes is consistent with the hypothesis that an increase in intracellular sodium could participate in the mechanism(s) of opioid tolerance development.
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004361:Drug Tolerance / Q000502:physiology*; D008954:Models, Biological; D009294:Narcotics / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology
D009294:Narcotics; D011957:Receptors, Opioid; D012964:Sodium