) Evidence suggests that phosphorylation of the dopamine D1 receptor is the triggering mechanism for desensitization. The experiments detailed in this proposal are designed to examine whether removal of dopamine D1 receptor potential phosphorylation sites alters agonist-induced desensitization. If phosphorylation of the dopamine D1 receptor is shown as necessary for desensitization, the potential phosphorylation sites will be added back, and the importance of each phosphorylation site(s) for agonist-induced desensitization investigated further. A second set of experiments will explore whether removal of potential phosphorylation sites alter subcellular localization. This will be studied with fluorescent microscopy using a dopamine D1 receptor fused with to N-terminal of the Green fluorescent protein. By understanding the molecular basis for desensitization of the dopamine D1 receptor, it may be possible to develop novel approaches to drug therapy for the treatment of Schizophrenia, and Parkinson's and Huntington's disease.
| Mason, John N; Kozell, Laura B; Neve, Kim A (2002) Regulation of dopamine D(1) receptor trafficking by protein kinase A-dependent phosphorylation. Mol Pharmacol 61:806-16 |
| Mason, J N; Eshleman, A J; Belknap, J K et al. (2001) NMDA receptor subunit mRNA and protein expression in ethanol-withdrawal seizure-prone and -resistant mice. Alcohol Clin Exp Res 25:651-60 |
