Biphasic amphetamine effects on skeletal muscle contractions: noncholinergic mechanisms

Noncholinergic mechanisms underlying the biphasic effects of (+)-amphetamine on skeletal muscle contractions were studied in the directly-stimulated, cholinergically blocked, rat phrenic nerve-diaphragm preparation. Low (2.7-8.1 x 10(-4)M) and high (10.8-21.6 x 10(-4)M) levels of (+)-amphetamine produced concentration-dependent enhancement and blockade of muscle contractions, respectively, in tissues pretreated with alpha-bungarotoxin, beta-bungarotoxin, or (+)-tubocurarine. These biphasic effects were not modified by tyramine, phentolamine, or propranolol arguing against a mechanism involving a direct or indirect adrenoceptor interaction. Amphetamine did not modify (Na+-K+)-stimulated ATPase activity. Increased [K+] or decreased [Na+] antagonized (+)-amphetamine enhancement of contractions and potentiated blockade; similar effects were observed after high concentration amantadine or procaine pretreatment. K+-free media potentiated (+)-amphetamine facilitation of contractions as did low concentrations of amantadine or procaine. These results suggest that amphetamine may biphasically modify skeletal muscle contractions by interactions involving the movements of Na+ and K+ independent of (Na+-K+)-stimulated ATPase.