Inhibition of tyrosine-3-monooxygenase by benserazide

Reinhard, John F.; Shearin, Mary D.

doi:10.1016/0006-2952(90)90433-l

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…Most of the strong TrpH inhibitors known are potential iron chelators, consistent with an essential role for the iron, as was discussed in section II.C.4. Generally, the inhibitors of this type that are of physiological interest are catechols, like the l -Dopa-derived TyrH catecholamine products or other compounds, such as benserazide, a catechol used in combination with l -Dopa as a Parkinson's treatment (Medopar). ,,,, Benserazide is competitive vs BH 4 ( K I = 80 ± 10 μM) and uncompetitive vs l -Trp ( K I = 176 ± 13 μM); similar results were obtained with TyrH . This result implies that this catechol and l -Trp do not bind the same form of TrpH; if benserazide binds to the free enzyme only, this could indicate some degree of order in the sequential mechanism.…”

Section: Trphmentioning

confidence: 56%

“…332,373,818,832,833 Benserazide is competitive vs BH 4 (K I ) 80 ( 10 µM) and uncompetitive vs L-Trp (K I ) 176 ( 13 µM); 367 similar results were obtained with TyrH. 834 This result implies that this catechol and L-Trp do not bind the same form of TrpH; if benserazide binds to the free enzyme only, this could indicate some degree of order in the sequential mechanism.…”

Section: Trphmentioning

confidence: 76%

See 1 more Smart Citation

Pterin-Dependent Amino Acid Hydroxylases

1996

Chem. Rev.

313

385

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Section: Trphmentioning

confidence: 56%

Section: Trphmentioning

confidence: 76%

Pterin-Dependent Amino Acid Hydroxylases

1996

Chem. Rev.

313

385

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“…Ro 4-4602 inhibits TH and tryptophan hydroxylase (EC I . 14.16.4) (Reinhard and Shearin, 1990;Johansen et al, I99 I), whereas NSD 10 15 has a mild M A 0 inhibitory effect (Carlsson et al, 1972). Moreover, the fluorinated analogues of DOPA do not produce other nonspecific actions such as reserpinelike monoamine depletion, inhibition of monoamine uptake, antagonism of adrenoceptors, or irreversible inhibition of catechol-0-methyltransferase (COMT; EC 2.1.1.6) (Jung et al, 1979a,b;Fozard et al, 1980;Palfreyman et al, 1984).…”

Section: Interest Of Dfmd As An Aadc Inhibitormentioning

confidence: 99%

Microdialysis Monitoring of 3,4‐Dihydroxyphenylalanine Accumulation After Decarboxylase Inhibition: A Means to Estimate In Vivo Changes in Tyrosine Hydroxylase Activity of the Rat Locus Ceruleus

Robert

Lambás‐Señas

Ortemann

et al. 1993

Journal of Neurochemistry

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An on-line microdialysis approach was developed to estimate changes in tyrosine hydroxylase activity in the locus ceruleus noradrenergic neurons of anesthetized rats by measuring the 3,4-dihydroxyphenylalanine (DOPA) accumulation in the extracellular fluid during perfusion of a n aromatic amino acid decarboxylase inhibitor through a dialysis probe. The aromatic amino acid decarboxylase inhibitor used was difluoromethyl-DOPA, which was shown to be more stable than NSD 10 15 or Ro 4-4602 in the perfusion fluid. A 1-h perfusion of a mol/L of difluoromethyl-DOPA solution induced a linear increase in DOPA concentration in the locus ceruleus dialysates that achieved a steady state within 1 h. The identity of DOPA accumulated in dialysates duringaromatic amino acid decarboxylase inhibition was confirmed by the disappearance ofthe chromatographic peak when DOPA formation was blocked by the administration ofa-methyl-p-tyrosine. Systemicadministration of the a,-antagonist piperoxane before difluoromethyl-DOPA perfusion markedly increased the DOPA concentration during both the accumulation and the steady-state periods, showing that the present technique is a suitable in vivo approach to monitor changes in tyrosine hydroxylase activity occurring in the locus ceruleus neurons. Key Words: Tyrosine hydroxyla~e-3~4-Dihydroxyphenylalanine-Locus ceruleus-Difluoromethyl-3,4-dihydroxyphenylalanine-Microdialysis-Piperoxane. Tyrosine hydroxylase (TH; EC 1.14.16.2, tyrosine-3-monooxygenase) catalyzes the formation of 3,4-dihydroxyphenylalanine (DOPA) from L-tyrosine, the rate-limiting step in noradrenaline biosynthesis. Rapid increases in TH activity have been observed in response to different stimuli of catecholaminergic neurons (review in Zigmond et al., 1989). Long-lasting increases in TH activity and/or concentration have been demonstrated in noradrenergic neurons of the rat locus ceruleus (LC) in a variety of physiological and pharmacological models including cold stress (Zigmond et al., 1974), reserpine treatment (Reis et al., 1975), inactivation of serotonin afferents (McRaeDegueurce and Pujol, 1979), and RU 24722 administration (Labatut et al., 1988). To investigate whether these changes in TH activity and concentration are functionally relevant, an in vivo method for determination of TH activity is needed. One approach is the measurement of in vivo 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in extracellular fluid, which have been shown to reflect changes in TH activity in noradrenergic neurons of the LC (Gonon et al., 1983). However, these measurements provide an indirect estimate of in vivo tyrosine hydroxylation. It was therefore more desirable to estimate changes in TH activity directly. For many years, such a determination has been achieved by measuring DOPA concentration in brain tissue homogenates after systemic ad-

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Measurement of tyrosine hydroxylase apoenzyme protein by enzyme-linked immunosorbent assay (ELISA): Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity and content

Reinhard

O’Callaghan

1991

Analytical Biochemistry

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Inhibition of tyrosine-3-monooxygenase by benserazide

Cited by 7 publications

References 12 publications

Pterin-Dependent Amino Acid Hydroxylases

Pterin-Dependent Amino Acid Hydroxylases

Microdialysis Monitoring of 3,4‐Dihydroxyphenylalanine Accumulation After Decarboxylase Inhibition: A Means to Estimate In Vivo Changes in Tyrosine Hydroxylase Activity of the Rat Locus Ceruleus

Measurement of tyrosine hydroxylase apoenzyme protein by enzyme-linked immunosorbent assay (ELISA): Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity and content

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