Interactions between GS and GI protein-coupled receptors and thei | 47898

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Interactions between GS and GI protein-coupled receptors and their potential role in pathophysiology and treatment of brain disorders

International Conference and Exhibition on Neurology & Therapeutics

May 14-16, 2012 Embassy Suites Las Vegas, USA

Eliyahu Dremencov

Accepted Abstracts: J Neurol Neurophysiol

Abstract :

I t was reported that GαS-coupled dopamine receptor D1 and adenosine receptor A2A form dimers with GαI-coupled adenosine receptor A1 and dopamine receptor D2 , respectively. Similar dimer is formed by D1 and D2 receptors. Since these dimers are GαQ-coupled, the dimerization might have strong functional output. GαS and GαI receptors play an important role in regulation of serotonin, norepinephrine and dopamine transmission. Since monoamines play an important role in pathophysiology of brain disorders, interactions between GαS and GαI-coupled receptors might be a target for CNS drugs. Indeed, co-activation of D1 and D2 receptors stimulates neuronal activity in pirifirm cortex and suppresses hippocampal synaptic plasticity, social interactions and working memory in rats. It suggests that interactions between D1 and D2 receptors play a role in age, memory and cognitive disorders. Activation of A2A receptors inhibits the firing activity of NE and DA neurons in locus coeruleus and ventral tegmental area, respectively. This inhibition reversed by subsequent blocking of A2A receptors and restored by administration of agonists of D2 or α2 -adrenoceptors. Antagonists of A2A receptors potentiate stimulatory effect of haloperidol on extracellular levels of NE and DA in prefrontal cortex and nucleus accumbens, respectively, and reduce haloperidol-induced catalepsy in rats. It suggests potential role of A2A/D2 and α2 -adrenoceptor interactions in schizophrenia. In conclusion, recent observations suggest that molecular and functional interactions between GαS and GαI-coupled receptors might be a common pattern playing an important role in pathophysiology and treatment of various CNS disorders.

Biography :

Dr Dremencov completed his BSc in Biology (1996) and MMedSc (2000) in Neurobiology in Hebrew University of Jerusalem. Performed PhD studies in Bar-Ilan University (2005, Israel) and Postdoctoral fellowship in the University of Ottawa, Canada (2007). Senior scientist in Brains On-Line BV, BMC Netherlands, and University of Groningen, the Netherlands (since 2008). Member of the International College of Neuropsychopharmacology (ICNP) and laureate of ICNP Rafaelson Prize (2006) and Honorary Mention (2008). Member of European College of Neuro-psychopharmacology (ECNP) and winner of ECNP (2008) and Society of Biological Psychiatry (2007) Fellowship Awards. Author of two books, six book chapters, and thirty-three (33) peer-reviewed manuscripts and more than fifty (50) congress presentations.