Richard DethProfessor of Pharmacology
- Department of Pharmaceutical Sciences
- School of Pharmacy
Office: 140 TF, Room 168
Ph.D. University of Miami
BS, State University of New York, Buffalo
Role of D4 dopamine receptors in schizophrenia and attention
My research focus has been directed toward understanding the molecular basis of transmembrane signaling by G protein-coupled receptors. This includes the study of their structure using three-dimensional molecular graphics and modeling how the binding of various drugs causes a shift in their conformational state. We are particularly interested in the spontaneous activity exhibited by some receptors. In the case of D4 dopamine receptors we have characterized their conformation-dependent participation in the process of phospholipid methylation, a unique and novel mechanism of signaling. A cycle of D4 receptor-mediated phospholipid methylation requires resupply of a new methyl group from the single carbon folate pool, thereby linking activity of the D4 receptor to folate-dependent pathways of cellular metabolism. Different methylation states of the D4 receptor exhibit various degrees of spontaneous activity with regard to G protein coupling. Deficits in D4 receptor-mediated phospholipid methylation may contribute to the etiology of several neuropsychiatric disorders, including schizophrenia and depression.
Deth, R.C. “Molecular Origins of Attention: The Dopamine-Folate Connection” Kluwer Academic Publishers (2003)
Zhu Q., Qi, L-J., Abou-Samra, A., Shi, A. and Deth, R.C.: “Protein kinase C-dependent constitutive activity of a2A/D-adrenergic receptors.” Pharmacol. 71: 80-90 (2004).
Waly, M., Banerjee, R., Choi, S.W., Mason, J., Benzecry, J., Power-Charnitsky, V.A, Deth, R.C. “PI3-kinase regulates methionine synthase: Activation by IGF-1 or dopamine and inhibition by heavy metals and thimerosal” Molecular Psychiatry 9: 358-370 (2004).