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Modulation of brain catecholamine absorbing proteins by dopaminergic agents
P I Modi1, A Kashyap, V D Nair
1Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
European Journal of Pharmacology
|March 28, 1996
Summary
Catecholamine absorbing proteins (CATNAPs) in the brain were purified and characterized. Their levels increase with catecholamine concentration, suggesting a protective role against neurodegenerative disease-related oxidative stress.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Catecholamine absorbing proteins (CATNAPs) are brain-localized proteins with unknown functions.
- Oxidative metabolism of catecholamines generates toxic free radicals implicated in neurodegenerative diseases like parkinsonism.
Purpose of the Study:
- To purify and pharmacologically characterize CATNAPs.
- To investigate the potential protective role of CATNAPs against catecholamine-induced oxidative stress.
Main Methods:
- Purification of CATNAPs using specific radioligands ([3H]N-n-propylnorapomorphine and [125I]DATN).
- Production of antibodies against purified CATNAPs (47, 40, and 26 kDa).
- Pharmacological modulation of CATNAP levels in rats using dopaminergic agents (L-DOPA, reserpine, dopamine, norepinephrine, etc.) and Western immunoblotting.
Main Results:
- Three CATNAPs (47, 40, 26 kDa) were identified and purified.
- L-DOPA and dopaminergic agents (dopamine, norepinephrine, apomorphine) increased CATNAP levels.
- Dopamine-depleting agent reserpine and neurotoxin 6-hydroxydopamine decreased CATNAP levels.
- CATNAP levels correlate positively with catecholamine concentration.
Conclusions:
- CATNAPs are pharmacologically modulated by dopaminergic agents.
- These findings suggest CATNAPs may play a cytoprotective role against oxidative stress in the brain.