Isolation, structure, and properties of the beta-carboline formed from 5-hydroxytryptamine by the superoxide anion-generating system.
A yellow substance was isolated by Sephadex LH-20 gel chromatography, silica gel TLC, and reversed-phase HPLC after incubation of 5-hydroxytryptamine (5-HT) with the superoxide anion (O2-)-generating system, i.e., the xanthine-xanthine oxidase system, in the presence of the Fe-EDTA complex and glycine in alkaline medium. The product gave a blue color with Ehrlich's reagent very slowly but no color with xanthydrol and Gibbs' reagent. Its reduced form, however, gave an immediate blue-violet color with all three reagents. No color was developed with ninhydrin, but the reduced form was orange-red. The chemical structure of the yellow substance was identified by 1H-nuclear magnetic resonance and field desorption-mass spectrometry as 4,9-dihydro-3H-pyrido[3,4-b]indol-6-ol (6-hydroxy-3,4-dihydro-beta-carboline, 5-hydroxy-2,3-dihydrotryptoline). The one carbon unit inserted into 5-HT came from glycine, with its 14C-2 being incorporated into C-1 of the yellow substance. The mechanism for the formation of the yellow substance from 5-HT is discussed. This compound inhibited 5-HT uptake into rat brain cortical synaptosomes with an IC50 of 1.5 X 10(-4) M and a Ki value of 1.2 X 10(-5) M.
Uemura
T
T
Division of Neurochemistry, Psychiatric Research Institute of Tokyo, Japan.
Kanashiro
M
M
Yamano
T
T
Hirai
K
K
Miyazaki
N
N
D000818:Animals; D000838:Anions / Q000378:metabolism; D002243:Carbolines / Q000096:biosynthesis / Q000302:isolation & purification*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005998:Glycine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013481:Superoxides / Q000096:biosynthesis*; D013574:Synaptosomes / Q000378:metabolism
D000838:Anions; D002243:Carbolines; D012702:Serotonin Antagonists; D013481:Superoxides; D012701:Serotonin; D005998:Glycine