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

Tom Lloyd, Brenda Boyd, Michael A. Walega, Barbara Jones Ebersole, Judith Weisz

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9 Scopus citations

Abstract

Abstract: 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 IC50 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 IC50 values of 30–600 nM.

Original languageEnglish (US)
Pages (from-to)948-954
Number of pages7
JournalJournal of neurochemistry
Volume38
Issue number4
DOIs
StatePublished - Apr 1982

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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