The role of adrenal hormones in the activation of tryptophan 2,3-dioxygenase by nicotinic acid in rat liver.
In this study, our previous finding that nicotinic acid activates tryptophan 2,3-dioxygenase as strongly as tryptophan was investigated in further detail. This study focused on the role of the adrenals in the activation process. Adrenalectomy abolished the activation due to nicotinic acid, but not the activation caused by tryptophan. The role of corticoids and/or adrenomedullary hormones in the enzyme activation was studied, by supplementing these hormones in adrenalectomized rats using minipumps implanted under the skin. The results showed that the enhanced activity of tryptophan 2,3-dioxygenase caused by nicotinic acid was partly restored by adrenaline following adrenalectomy but not by corticosterone supplementation. The results were supported by further experiments in which the rats were treated with adrenaline or corticosterone intraperitoneally before nicotinic acid administration. The conclusion that adrenaline participates in the regulation of tryptophan 2,3-dioxygenase should promote further study to determine whether adrenaline is a general modulator of this enzyme. This experimental model generated new information on the activation mechanism of tryptophan 2,3-dioxygenase by nicotinic acid.
Sainio
E L
EL
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D009525:Niacin / Q000494:pharmacology*; D051381:Rats; D014364:Tryptophan / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D009525:Niacin; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D003345:Corticosterone; D004837:Epinephrine