Acute administration of cocaine regulates the phosphorylation of serine-19, -31 and -40 in tyrosine hydroxylase
| Autor: | Jakub P, Jedynak, Syed F, Ali, John W, Haycock, Bruce T, Hope |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Binding Sites Dose-Response Relationship Drug Tyrosine 3-Monooxygenase Blotting Western Ventral Tegmental Area Brain Amygdala Nucleus Accumbens Dihydroxyphenylalanine Rats Enzyme Activation Rats Sprague-Dawley Cocaine Serine Animals Aromatic Amino Acid Decarboxylase Inhibitors Caudate Nucleus Enzyme Inhibitors Phosphorylation Injections Intraperitoneal |
| Zdroj: | Journal of neurochemistry. 82(2) |
| ISSN: | 0022-3042 |
| Popis: | Acute cocaine can inhibit catecholamine biosynthesis by regulating the enzymatic activity of tyrosine hydroxylase via alterations in the phosphorylation state of the enzyme. The mechanisms underlying acute cocaine-dependent regulation of tyrosine hydroxylase phosphorylation have not been determined. In this study, 0, 15 or 30 mg/kg cocaine was administered intraperitoneally to rats and the phosphorylation state of tyrosine hydroxylase in the brain was examined using antibodies specific for the phosphorylated forms of serine-19, -31 and -40 in tyrosine hydroxylase. In the caudate and nucleus accumbens, cocaine dose-dependently decreased the levels of phosphorylated serine-19, -31 and -40. In the ventral tegmental area, the levels of phosphorylated serine-19, but not serine-31 and -40, were decreased by 15 and 30 mg/kg cocaine. In the amygdala, the levels of phosphorylated serine-19, but not serine-31 or -40, were decreased. The functional effects of these alterations in phosphorylation state were assessed by measuring tyrosine hydroxylase activity in vivo (accumulation of DOPA after administration of the decarboxylase inhibitor NSD-1015). Acute administration of 30 mg/kg cocaine significantly decreased l-DOPA production in caudate and accumbens but not in amygdala. These data suggest that the phosphorylation of serine-31 or -40, but not serine-19, is involved in the regulation of tyrosine hydroxylase activity by acute cocaine. |
| Databáze: | OpenAIRE |
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