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Acute administration of cocaine regulates the phosphorylation of serine‐19, ‐31 and ‐40 in tyrosine hydroxylase
Author(s) -
Jedynak Jakub P.,
Ali Syed F.,
Haycock John W.,
Hope Bruce T.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00982.x
Subject(s) - tyrosine hydroxylase , phosphorylation , serine , endocrinology , medicine , tyrosine , nucleus accumbens , chemistry , dopamine , tyrosine phosphorylation , biochemistry , biology
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.