Modulation of a 40-kDa catecholamine regulated protein by dopamine receptor antagonists.
Previous reports have shown that catecholamine regulated proteins (CRP) are central nervous system specific and covalently bind to catecholamines. In the present study, we report the subcellular localization and differential modulation of a 40-kDa catecholamine regulated protein (CRP40) by dopamine D1 and D2 receptor antagonists. CRP40 was found to be localized with nuclear and synaptosomal/mitochondrial and fractions. Chronic treatment with dopamine D2 receptor antagonist haloperidol in rats significantly increased the levels of CRP40 in the striatum, whereas, chronic R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) dopamine D1 receptor antagonist administration significantly decreased striatal CRP40 levels. Moreover, acute haloperidol treatment did not alter the levels of CRP40 in any of the brain regions. Despite a sequence homology with the heat shock protein 70 (HSP70), levels of HSP70 remained unchanged after either drug treatment, suggesting a distinct function of CRP40 than HSP70. These results further suggest that CRP40 play an important role in dopaminergic neuronal function and the dopamine D1 receptor-mediated signaling pathway may be involved in the regulation of CRP40.
Sharan
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Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, HSC 4N78, Hamilton, Ontario, Canada L8S 3Z5.
Nair
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Mishra
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RK
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001552:Benzazepines; D018492:Dopamine Antagonists; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; C422207:catecholamine-regulated protein, 40 kDa; D011433:Propranolol; D006220:Haloperidol