DOPA Levels Research Articles

Norepinephrine and DOPA decar☐ylase in rat brain following hypothalamic lesions

Lateral hypothalamic lesions transecting the fibers of the medial forebrain bundle in the rat decrease by 52% the norepinephrine content of the telencephalon but have no effect on brainstem levels of the amine. Lateral hypothalamic lesions also produce a 36% decrease in the telencephalic level of aromatic l-amino acid decar☐ylase measured in vitro as 3,4-dihydroxyphenylalanine (DOPA) decar☐ylase. Medial hypothalamic lesions, in contrast, do not alter either brain norepinephrine levels or telencephalic DOPA decar☐ylase activity. These findings indicate that the maintenance of normal levels of norepinephrine and DOPA decar☐ylase activity in the rat telencephalon is dependent upon the integrity of the medial forebrain bundle within the lateral hypothalamus.

On the role of pteridines as cofactors for tyrosine hydroxylase

Dithiocarbamates and CS2 have been associated with neurobehavioural changes suggestive of central dopaminergic dysfunction. Diethyldithiocarbamate (DEDC), dimethyldithiocarbamate (DMDC), and methyldithiocarbamate (MDC) were examined for their ability to inhibit tyrosine hydroxylase (TH) activity in PC12 cells and transfected CHO fibroblasts that expressed TH (CHOTH) activity when tetrahydrobiopterin (BH4) was added to medium. DEDC or DMDC did not significantly alter viability of PC12 cells or CHOTH cells at ≤100 μM for 18 h; the EC50 for each compound was approximately 5 mM in both cell lines. In contrast, the EC50 for MDC was 41 or 74 μM in PC12 or CHOTH cultures, respectively. There was no change in immunodetectable levels of TH in PC12 or CHOTH cells following exposure to subcytotoxic concentrations of dithiocarbamates. DEDC and DMDC (5 to 100 μM) produced concentration-dependent reductions in PC12 cell dopamine and dopac levels as well as in dopa levels in CHOTH cultures. Reduction of PC12 catechols was not due to altered vesicular storage. In vitro PC12 TH activity was 80.2 ± 3.4% or 82.4 ± 2.9% of control following exposure to 100 μM DEDC or DMDC, respectively, and was not fully restored by incubation with Fe2+. These results show that DEDC and DMDC, but not MDC, are low potency cytotoxins that decrease TH activity in cultured cells through mechanisms other than inhibition of BH4 biosynthesis or iron chelation.

Metabolism of dopa- 14C in the normal and α-methyldopa-treated mouse

Intraperitoneally injected dl-3, 4-dihydroxyphenylalanine (dopa)-α- 14C was rapidly metabolized in the intact mouse; the biological half-life was approximately 15 min. Decar☐ylation constituted an important but not the only route of metabolism. One hour after the administration of dopa- 14C the following labeled catechols were found in whole mouse homogenates (concentrations expressed as a percentage of total recovered radioactivity): dopa (17.3%), dopamine (13.8%), norepinephrine (1.2%), epinephrine (0.5%), 3,4-dihydroxyphenylacetic acid (dopac) (0.8%). α-Methyldopa, injected intraperitoneally in a dose of 3.12 mg/kg, inhibited the decar☐ylation in vivo of dopa- 14C. Larger doses resulted in progressively greater inhibition; maximal response was obtained with 50 mg/kg. In mice given α-methyldopa (25 mg/kg) 30 min prior to dopa- 14C and sacrificed 1 hr later, the dopa level was increased (30.6%), and the dopamine level was reduced (3.8%). The duration in vivo of the decar☐ylase inhibitory activity of α-methyldopa in the mouse was 8 to 16 hr.