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  • Title: The inhibitory role of methylation on the binding characteristics of dopamine receptors and transporter.
    Author: Lee ES, Chen H, Shepherd KR, Lamango NS, Soliman KF, Charlton CG.
    Journal: Neurosci Res; 2004 Mar; 48(3):335-44. PubMed ID: 15154679.
    Abstract:
    Excess methylation has been suggested to play a role in the pathogenesis of Parkinson's disease (PD), since the administration of S-adenosylmethionine (SAM), a biological methyl donor, induces PD-like changes in rodents. It was proposed that SAM-induced PD-like changes might be associated with its ability to react with the dopaminergic system. In the present study the effects of SAM on dopamine receptors and transporters were investigated using rats and cloned dopamine receptor proteins. Autoradiographic examination of SAM indicated its tendency to be localized and accumulated in rat striatal region after the intracerebroventricular injection into rat brain. Moreover, results showed that SAM significantly decreased dopamine D1 and D2 receptor binding activities by decreasing the Bmax and increasing the Kd values. At concentrations of 0.1, 0.25 and 0.5 mM, SAM was able to reduce the Bmax from the control value of 848.1 for dopamine D1-specific ligand [3H] SCH 23390 to 760.1, 702.6 and 443.0 fmol/mg protein, respectively. At the same concentrations, SAM was able to increase the Kd values from 0.91 for the control to 1.06, 3.84 and 7.01 nM of [3H] SCH 23390, respectively. The effects of SAM on dopamine D2 binding were similar to those of dopamine D1 binding. SAM also decreased dopamine transporter activity. The interaction of SAM with dopamine receptor proteins produced methanol from methyl-ester formation and hydrolysis. We propose that the SAM effect might be related to its ability to react with dopamine receptor proteins through methyl-ester formation and methanol production following the hydrolysis of the carboxyl-methylated receptor proteins.
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