title: N-methylisoquinolinium ion as an inhibitor of tyrosine hydroxylase, aromatic l-amino acid decarboxylase and monoamine oxidase.
abstract: The effect of the N-methylisoquinolinium ion (NMIQ(+)) on the activity of enzymes related to metabolism of dopamine was studied using a rat clonal pheochromocytoma PC12h cell line. The activities of tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were inhibited by NMIQ(+), but the mechanism of inhibition of these enzymes differed from each other. TH activity in the cells was inhibited by NMIQ(+) with an IC(50) of about 75 ?M. Aromatic l-amino acid decarboxylase (AADC) was also inhibited by NMIQ(+) but in competition with a co-factor, pyridoxal-5-phosphate, and the K(i) value was 90 ?M. MAO was inhibited by NMIQ(+) in competition with a substrate, kynuramine, and the K(i) value was 20 ?M. In vivo effects of NMIQ(+) on these enzymes in PC12h cells were examined by culture of the cells in the presence of 100 nM-1 mM NMIQ(+) for 6 days. After 6 days culture, TH activity was reduced in cells cultured with NMIQ(+) at concentrations higher than 10 ?M, but the activities of AADC and MAO were reduced only in cells cultured with 1 mM NMIQ(+). In addition, NMIQ(+) was transported into the cells by a transport system specific for dopamine. These data suggest that NMIQ(+) may perturb the catecholamine metabolism of a dopaminergic system in the brain, as a naturally-occurring compound.
authors.affiliation: Department of Biochemistry, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Naoi
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Parvez
authors.forename: R
authors.initials: R
authors.lastname: Kabeya
authors.forename: E
authors.initials: E
authors.lastname: Taguchi
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: T
authors.initials: T
authors.lastname: Nagatsu