Premium
A Comparison of 2‐Hydroxyestradiol and U‐0521 (3′4′‐Dihydroxy‐2‐methylpropiophenone, Upjohn) as In Situ and In Vitro Inhibitors of Tyro sine Hydroxylase
Author(s) -
Lloyd Tom,
Boyd Brenda,
Walega Michael A.,
Ebersole Barbara Jones,
Weisz Judith
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb05334.x
Subject(s) - tyrosine hydroxylase , catechol , catecholamine , chemistry , in vitro , tyrosine 3 monooxygenase , enzyme , biochemistry , biology , endocrinology
Feedback inhibition of tyrosine hydroxylase by catechols was evaluated using in situ and in vitro enzyme assays. The three catechol compounds used were norepinephrine, 2‐hydroxyestradiol, and 3′4′‐dihydroxy‐2‐methylpropiophenone (U‐0521, Upjohn); representing endogenous catechol‐amines, catechol estrogens, and a synthetic catechol, respectively. The in situ experiments were performed with dissociated retinal cells from rats and with stationary phase adrenergic‐like neuroblastoma cells (N1E‐115). The catechol estrogen, 2‐hydroxyestradiol, resembled the endogenous catecholamines in its potency to inhibit in vitro and in situ tyrosine hydroxylations with IC 50 values of 10 μM in vitro and 100 μM in situ. The drug U‐0521, which has been used as an inhibitor of catechol‐ O ‐methyltransferase (COMT), was also found to be an inhibitor of tyrosine hydroxylase. Further, it was shown to be more potent than the natural catechols, both in vitro and in situ , with IC 50 values of 30–600 nM.