Amphetamine-induced alterations in the target enzymes: Possibility of a dual role in adaptation

Single d-amphetamine administration inhibited the specific activities of three membrane-bound enzymes from rat brain microsome viz. Na⁺-K⁺-Mg⁺²-ATPase, acetylcholinesterase (AchE) and glutamine synthetase (GS). A dichotomy was observed in the response of these enzymes to chronic drug treatment: Na⁺-K⁺-Mg⁺²-ATPase returned to control levels while AchE and GS activities showed significant increases. This paper proposed the idea that such dynamic reorientations might alleviate the initial drug action through 'localized scavenging' of the drug within the biophase. While higher amounts of AchE and GS are capable of binding more (as compared to acute) drug sparing, simultaneously, sufficient enzyme molecules for routine biological function, the desensitized form of Na⁺-K⁺-Mg⁺²-ATPase could have an augmented affinity for the drug molecule remaining, at the same time, unperturbed by drug binding. The realization of a teleological adaptive strategy within the framework of apparently diverse enzymatic responses is discussed with special reference to drug tolerance.