Biomedical subjects

H L Wiener

Publications and source records attributed to H L Wiener.

24 records · Page 2Linked to original sources

PubMed1989

Dopamine D1 receptor and dopamine D2 receptor binding activity changes during chronic administration of nicotine in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.

The effect of nicotine on MPTP-induced changes in striatal dopamine receptors binding activity was investigated. Dopamine D1 and D2 receptors were labeled with [3H]SCH-23390 and [3H]spiperone respectively in BALB/cBy mice. With administration of only MPTP, which caused more than an 80% decrease in striatal dopamine level, binding of 0.15 nM [3H]spiperone was increased by 37%; whereas 0.3 nM [3H]SCH-23390 binding was unchanged. With chronic nicotine treatment (0.4 mg/kg twice daily for 7-9 days), [3H]SCH-23390 binding activity was increased by 27% and [3H]spiperone binding activity was unchanged. When nicotine was administered after MPTP, their separate effects could be seen in that both the D1 and D2 dopamine receptor ligand binding activities were increased and that nicotine elevated the ratio of D1/D2 receptor binding activities in MPTP-treated mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Ascorbic acid inhibits [3H]SCH-23390 binding to striatal dopamine D1 receptors.

The present study describes the inhibition of [3H]SCH-23390 binding to striatal dopamine D1 receptors in the presence of ascorbic acid. Specific [3H]SCH-23390 binding was maximally inhibited by 0.1 mM ascorbic acid. As determined by Scatchard analysis the binding in the presence of 0.01, 0.1, or 10 mM ascorbic acid was consonant with non-competitive inhibition with a 26%, 38%, or 19% decrease, respectively, in the maximal number of binding sites; the affinity of these binding sites was not affected. Inhibition of [3H]SCH-23390 binding by ascorbic acid was reversible; striatal homogenates incubated with 0.1 mM ascorbic acid and subsequently washed free of ascorbic acid had the same Scatchard parameters as untreated preparations.

Animals↗

PubMed1989

Oxidative metabolism of cocaine: comparison of brain and liver.

Norcocaine (NC) and N-hydroxynorcocaine (NHNC), products of the oxidative metabolism of cocaine, were examined in plasma, brain, and liver of mice injected intraperitoneally with cocaine. Plasma levels of NHNC were altered in vivo by inhibiting esterase activity with diazinon and chloral hydrate or activating esterase activity with phenobarbital, and activating the microsomal P-450 system with phenobarbital. Changes in plasma concentrations of NHNC resulted in similar changes in brain, which were often different from those in liver. After intracisternal administration of cocaine to mice, no appreciable amount of NC or NHNC could be detected in brain; the same results were obtained upon intracisternal and intraventricular administration to rats. Microsomal preparations from mouse brain were found to be considerably less active than those from liver in converting NC to NHNC. We conclude that the cerebral oxidative metabolism of cocaine is not appreciable and that most of the NC and NHNC found in the brain after systemic cocaine administration is derived from plasma rather than formed centrally by brain microsomal enzymes.

Animals↗

PubMed1988

Effect of chronic oral nicotine on dopaminergic function in the MPTP-treated mouse.

Although epidemiological studies have suggested a lower incidence of Parkinson's disease in cigarette smokers, repeated exposure to cigarette smoke or nicotine does not protect against neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since there is some evidence that nicotinic antagonists, nicotine, and neurotransmitters may have tropic effects on neurite outgrowth, the present study examined the effects of chronic nicotine administration for 16 weeks (in drinking water; 5 mg/kg consumed per day) on the rate of terminal recovery after striatal lesioning with MPTP (2 x 30 mg/kg, s.c.). Terminal recovery, as measured by the rate of recovery in the level of striatal dopamine, was not affected by nicotine. Monoamine oxidase-B activity was not reduced by MPTP, nor did nicotine affect its activity in striatal homogenates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1987

Inactivation of gamma-glutamylcysteine synthetase, but not of glutamine synthetase, by S-sulfocysteine and S-sulfohomocysteine.

The reactions catalyzed by gamma-glutamylcysteine synthetase and glutamine synthetase are thought to proceed via enzyme-bound gamma-glutamyl phosphate intermediates. We investigated the possibility that S-sulfocysteine and S-sulfohomocysteine might act as analogs of gamma-glutamyl phosphate or of the associated putative tetrahedral intermediates. The D- and L-enantiomers of S-sulfocysteine and S-sulfohomocysteine were found to rapidly inactivate rat kidney gamma-glutamylcysteine synthetase but to be reversible inhibitors of sheep brain glutamine synthetase. Inactivation of gamma-glutamylcysteine synthetase does not require ATP and is associated with noncovalent binding of close to 1 mol of inactivator/mol of enzyme. The findings indicate that the S-sulfo amino acids are transition-state analogs, and that binding of S-sulfo amino acid to the enzyme induces formation of a very stable enzyme-inactivator complex. The data suggest that stabilization of the enzyme-inactivator complex results from interactions involving the sulfenyl sulfur atom of the S-sulfo amino acid and the active site thiol group of the enzyme.

Animals↗

PubMedDate not supplied

Chronic treatment of aged mice with L-deprenyl produces marked striatal MAO-B inhibition but no beneficial effects on survival, motor performance, or nigral lipofuscin accumulation.

Male C57BL/6J mice were provided I-deprenyl (at 0, 0.5 mg/kg or 1.0 mg/kg per day) in their drinking water beginning at 18 months of age. A battery of motor tests, including open-field, tightrope, rotorod, inclined screen, runwheel, and rotodrum tests, was administered before treatment and then 6 months later at 24 months of age. A subsample of mice was retested again at 27 months of age. An untreated group of 9-month-old mice served as young controls. Deprenyl treatment reduced striatal MAO-B activity by up to 60% after 6 months on treatment but had no significant effects on striatal catecholamine levels. No significant effects of deprenyl treatment were observed on body weight, fluid intake, or survival of the mice. Chronic deprenyl treatment also did not affect motor performance in any test, except rotodrum performance at 27 months of age, which was significantly better in the 1.0 mg/kg group treated group compared to controls. No age or deprenyl effects were observed with respect to cell counts in the substantia nigra. However, nigral cells containing lipofuscin increased with age, but this neurohistochemical parameter was also unaffected by deprenyl treatment.

Aging↗