Differential species sensitivity to the inhibitory effect of cardiac glycosides on 3H-1-noradrenaline accumulation by tissue slices.
Effects of three cardiac glycosides on the accumulation of 3H-1-noradrenaline (3H-1-NA) by slices of heart and spleen were studied. Ouabain, digitoxin and digoxin, all produced a concentration dependent inhibition of 3H-1-NA uptake in both types of tissue slices. The maximum amount of 3H-1-NA accumulated as well as the rate of uptake was decreased. Digitoxin and ouabain were equipotent; however, digoxin was significantly less potent. Tissues from different mamalian specis did not exhibit the same degree of sensitivity to the inhibitory effect of cardiac glycosides on 3H-1-NA accumulation. Dogs were most sensitive and guinea-pigs an order of magnitude less sensitive. Rats were least sensitive by roughly two orders of magnitude when compared with guinea-pigs. The relationship of the effect of digitalis on 3H-1-NA accumulation to digitalis-induced cardiac arrhythmias is discussed. Finally, the pattern of species sensitivity found here is compared with that observed in relation to inhibition of Na+-K+-ATPase by cardiac glycosides.
D000818:Animals; D002301:Cardiac Glycosides / Q000494:pharmacology*; D003864:Depression, Chemical; D004074:Digitoxin / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002301:Cardiac Glycosides; D006892:Hydroxydopamines; D010042:Ouabain; D004077:Digoxin; D004074:Digitoxin; D009638:Norepinephrine