Effects of biogenic aldehydes and aldehyde dehydrogenase inhibitors on rat brain tryptophan hydroxylase activity in vitro.
The effect of indole-3-acetaldehyde, 5-hydroxyindole-3-acetaldehyde, disulfiram, diethyldithiocarbamate, coprine, and 1-amino-cyclopropanol on tryptophan hydroxylase activity was studied in vitro using high performance liquid chromatography with electro-chemical detection. With the analytical method developed, 5-hydroxytryptophan, serotonin, and 5-hydroxyindole-3-acetic acid could be measured simultaneously. Indole-3-acetaldehyde (12-1200 microM) was found to cause a 6-33% inhibition of the enzyme. Dependent upon the nature of the sulfhydryl- or reducing-agent (dithiotreitol, glutathione, or ascorbate) present in the incubates, the degree of inhibition by disulfiram varied, probably due to the formation of various mixed disulfides. Also the presence of diethyldithiocarbamate (160-1600 microM) was found to inhibit tryptophan hydroxylase (28-91%), while 5-hydroxyindole-3-acetaldehyde, coprine, or 1-aminocyclopropanol appeared to have no effect on the enzyme activity.
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*
D000447:Aldehydes; D003521:Cyclopropanes; D007211:Indoles; C014318:1-aminocyclopropanol; D005973:Glutamine; C004277:hydroxyindoleacetaldehyde; C001655:indole-3-acetaldehyde; C014423:coprine; D006897:Hydroxyindoleacetic Acid; D004050:Ditiocarb; D014446:Tyrosine 3-Monooxygenase; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram