RGS9-2: probing an intracellular modulator of behavior as a drug target.
Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction. This protein negatively modulates signal transduction thus playing a key part in striatal function and resultant behavioral responses. In particular, there is evidence of important interactions with mu-opioid- and dopamine D(2)-receptor signaling pathways. Several studies indicate that manipulations of RGS9-2 levels in the striatum might greatly affect pharmacological responses. These findings indicate that treatment strategies targeting RGS9-2 levels or activity might be used to enhance responses to drugs acting at GPCRs and/or prevent undesired drug actions.
Traynor
John R
JR
Department of Pharmacology and Substance Abuse Research Center, University of Michigan, Ann Arbor, MI 48109, USA.
Terzi
Dimitra
D
Caldarone
Barbara J
BJ
Zachariou
Venetia
V
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D009293:Opioid-Related Disorders / Q000378:metabolism / Q000523:psychology; D020710:RGS Proteins / Q000096:biosynthesis / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology; D012201:Reward; D015398:Signal Transduction
D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D020710:RGS Proteins; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D017450:Receptors, Opioid, mu; C116925:regulator of g-protein signaling 9