Augmentation of the indirect sympathomimetic action of tyramine by cardioactive steroids is a consequence of elevated intracellular sodium.
The augmentation by the cardioactive steroid acetylstrophanthidin of neurotransmitter release evoked by tyramine, and the dependence of the augmentation upon Na+, has been investigated in dog saphenous vein rings in which monoamine oxidase activity and uptake2 had been inhibited with pargyline and corticosterone respectively. High extracellular Na+ (Nao; 263 mmol/l) reduced basal efflux of 3H-compounds from the rings and also reduced tyramine-evoked efflux. Low Nao (25 mmol/l) increased basal efflux of 3H but reduced tyramine-evoked efflux. The increment in basal 3H-efflux caused by low Nao was cocaine-sensitive. A presumed increase in intracellular Na+ (Nai), produced by preincubating rings with acetylstrophanthidin in normal (143 mmol/l) or high Nao, augmented 3H-efflux evoked by subsequent incubation with tyramine in normal Nao. Pre-incubating rings with acetylstrophanthidin in low Nao, conditions which would not be expected to increase Nai, did not cause augmentation of the subsequent tyramine-evoked 3H-efflux. An increase in Nai, produced either as above or by pre-incubating rings in high Nao alone, reduced subsequent neuronal 14C-tyramine uptake. Low Nao present only during incubation reduced neuronal 14C-tyramine uptake, but high Nao present only during incubation did not increase neuronal 14C-tyramine uptake from that measured in normal Nao. The data are consistent with the following hypotheses: that tyramine uptake is dependent upon the prevailing inwardly directed Na+-gradient, that consequent noradrenaline efflux is Na+-gradient dependent and that the enhancement by acetylstrophanthidin of tyramine-evoked 3H-efflux is a consequence of the raised Nai caused by Na+,K+-ATPase inhibition.
D000818:Animals; D002301:Cardiac Glycosides / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000502:physiology*; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D013566:Sympathomimetics; D014439:Tyramine / Q000378:metabolism / Q000494:pharmacology*
D002301:Cardiac Glycosides; D018377:Neurotransmitter Agents; D013566:Sympathomimetics; D013327:Strophanthidin; D012964:Sodium; D003042:Cocaine; C004681:acetylstrophanthidin; D014439:Tyramine