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Dopamine D 2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse
Author(s) -
Oien Derek B.,
Ortiz Andrea N.,
Rittel Alexander G.,
Dobrowsky Rick T.,
Johnson Michael A.,
Levant Beth,
Fowler Stephen C.,
Moskovitz Jackob
Publication year - 2010
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 - 10.1111/j.1471-4159.2010.06721.x
Subject(s) - dopamine , knockout mouse , agonist , receptor , medicine , dopamine receptor d1 , dopamine receptor , endocrinology , methionine , chemistry , biology , biochemistry , amino acid
J. Neurochem. (2010) 114 , 51–61. Abstract Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio‐behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D 2 ‐receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed, protein expression levels of dopamine D 2 ‐receptor were higher in knockout mice compared with wild‐type. However, the binding of dopamine D 2 ‐receptor agonist was compromised in the same fractions of knockout mice. Coupling efficiency of dopamine D 2 ‐receptors to G‐proteins was also significantly reduced in knockout mice, supporting the compromised agonist binding. Furthermore, pre‐synaptic dopamine release in knockout striatal sections was less responsive than control sections to dopamine D 2 ‐receptor ligands. Behaviorally, the locomotor activity of knockout mice was less responsive to the inhibitory effect of quinpirole than wild‐type mice. Involvement of specific methionine residue oxidation in the dopamine D 2 ‐receptor third intracellular loop is suggested by in vitro studies. We conclude that ablation of methionine sulfoxide reductase can affect dopamine signaling through altering dopamine D 2 ‐receptor physiology and may be related to symptoms associated with neurological disorders and diseases.