Inhibition of tryptophan hydroxylase by (R)- and (S)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines (salsolinols).
The (R)- and (S)-enantiomers of salsolinol, the dopamine-derived tetrahydroisoquinolines, were found to inhibit the activity of tryptophan hydroxylase (TPH), prepared from serotonin-producing murine mastocytoma P-815 cells. Inhibition of TPH by salsolinols was found to be non-competitive with the substrate L-tryptophan. Tryptophan hydroxylase is composed of two elements with different kinetic properties in terms of cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin and these two elements were inhibited by salsolinols in competitive and uncompetitive ways, respectively. Stereoselectivity of salsolinol was not observed, concerning the potency and the type of inhibition on PTH. These data indicate that salsolinols might be naturally occurring inhibitors of indoleamine metabolism.
Ota
M
M
Department of Psychiatry, Nagoya City University School of Medicine, Japan.
Dostert
P
P
Hamanaka
T
T
Nagatsu
T
T
Naoi
M
M
D000818:Animals; D002460:Cell Line; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D012515:Mast-Cell Sarcoma; D051379:Mice; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
D007546:Isoquinolines; C036617:salsolinol; D014365:Tryptophan Hydroxylase