title: Biphasic amphetamine effects on skeletal muscle contractions: noncholinergic mechanisms.
abstract: 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.
mesh_terms: D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D003620:Dantrolene / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009121:Muscle Denervation; D009638:Norepinephrine / Q000502:physiology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D011343:Procaine; D000547:Amantadine; D000254:Sodium-Potassium-Exchanging ATPase; D003620:Dantrolene; D003913:Dextroamphetamine; D009638:Norepinephrine