Age-related changes in the chronotropic effect and the enzymic decarboxylation of L-threo-3,4-dihydroxphenylserine in the rat heart.
The cardiac effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) and the enzymatic decarboxylation of the drug by L-aromatic amino acid decarboxylase (AADC) were studied in atria isolated from rats ranging in age from newborn to adults and the findings compared with the cardiac effect of noradrenaline (NA). L-threo-DOPS produced dose-dependent, slow-onset and positive chronotropic effects in atria from rats of different ages. Its effect was inhibited in atria from benserazide-treated rats, suggesting that the effects are due to NA formed from L-threo-DOPS by enzymic decarboxylation rather than to the compound itself. Chronotropic sensitivity to L-threo-DOPS was highest in the newborn and decreased with age during the first 3 weeks of life. The development of cardiac response to it correlated well with the development of enzymic decarboxylation of the drug that did not correlated with the developments of chronotropic sensitivity to NA and of NA concentrations in the heart. These findings suggest that in newborn rats, L-threo-DOPS is effectively converted by AADC to NA which in turn acts on beta-receptors in the pacemaker cell membrane.
D000367:Age Factors; D000818:Animals; D003653:Decarboxylation; D015103:Droxidopa / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000031:analogs & derivatives*; D013237:Stereoisomerism
D012694:Serine; D015103:Droxidopa; D009638:Norepinephrine