ISSN:
1432-1912
Keywords:
Tyrosine hydroxylase
;
Feedback inhibition
;
Dopamine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Several drugs with a catechol moiety were studied for their potency to inhibit tyrosine hydroxylase (TH) from PC-12 cells in vitro. When the natural compounds tested were compared, dopamine, norepinephrine and 2(3,4-dihydroxyphenyl)-ethanol (DOPET) were most effective (IC50 between 1.4 and 3.6 μM with 0.5 μM 6(R,S)-l-erythro-5,6,7,8-tetrahydrobiopterin as cofactor). 3,4-Dihydroxyphenylalanine (DOPA; IC50: 35 μM) and 3,4-dihydroxyphenylacetic acid (DOPAC; IC50: 180 μM were less potent inhibitors. Among the synthetic drugs possessing catechol moiety, isoproterenol, (±)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) and (±)-2-dimethylamino-6,7-dihydroxy-tetrahydronaphthalene (TL-99) had the same inhibitory effects as the natural catecholamines (IC50 between 1.6 and 3.9 μM), whereas the apomorphine derivatives and 2,3,4,5-tetrahydro-1-phenyl-1 H-3-benzazepine-7,8-diol (SKF 38393) were even more potent (IC50: 0.5–0.8 μM). These results demonstrate that natural catechols and certain drugs (e.g. 6,7-ADTN, TL-99, SKF 38393) are more effective direct blockers of tyrosine hydroxylase than generally assumed provided appropriate assay conditions are used. In the case of dopamine and norepinephrine, these findings suggest a reevaluation of their role for feedback control of tyrosine hydroxylase in vivo.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00500085
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