Signal Transduction Pathways Modulated by D2-Like Dopamine Receptors

Abstract

Publisher Summary he D2-like subfamily of dopamine receptors is a target for drugs used to treat Parkinson's disease and schizophrenia. Dopamine receptors regulate ion channels to affect the excitability of neurons and turn on second-messenger systems to activate protein kinase cascades and transcription factors for long-term effects on gene expression. Characterization of the early events triggered by activation of dopamine receptors at a molecular level can contribute to an understanding of how changes in ion channel activation, protein phosphorylation, and alterations in the phenotype of the cells can occur. The D2 subfamily includes D2A, D2B, D3, and D4 receptors. D2A and D2B receptors are isoforms encoded by a single gene, which is differentially spliced to include (D2A) or exclude (D2B) 29 amino acids within the third intracytoplasmic loop. All of the D2-like receptors are members of the G-protein-linked superfamily of receptors, and in native tissues most if not all D2-like receptor signaling is blocked by pertussis toxin, implicating linkage to the Gi/o proteins. The capacity for D2 receptors to activate mitogen-activated protein kinase (MAPK) implies a role for dopamine in synaptic remodeling. These potential novel aspects of dopaminergic neurotransmission are considered as important aspects of Parkinson's disease and antipsychotic therapy.