Inhibition of hepatic tryptophan-2,3-dioxygenase: superior potency of melatonin over serotonin.
In view of the biogenic amine deficiency hypothesis of depression and the contentious claim that hepatic tryptophan-2,3-dioxygenase (TDO) is the major peripheral determinant of brain tryptophan, brain serotonin (5-HT), and ultimately melatonin, the regulation of TDO by melatonin and 5-HT is investigated and discussed. It is concluded that TDO activity is regulated differentially by melatonin and 5-HT. Melatonin is a competitive inhibitor of TDO and 5-HT is predominantly an allosteric inhibitor. In the presence of 5-HT the effects of melatonin are nullified. However melatonin alone is a more potent inhibitor of TDO. Melatonin is also shown to be a reversible negative effector of TDO.
Walsh
H A
HA
University of Fort Hare, Alice, South Africa. walsh@ufhcc.ufh.ac.za
Daya
S
S
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000201:enzymology*; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D012701:Serotonin; D014366:Tryptophan Oxygenase; D008550:Melatonin