Preliminary Study On The ERK/MAPK Signal Transduction Induced By GABA_B Receptor In Cerebellar Granule Neurons

γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). GABAB receptors are the metabotropic GABA receptors and belong to Family C G protein-coupled receptors. They are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. In present study, neural GABAB receptors effect on the adenylate cyclase system and Ca2+ and K+ ion channels thought activate Gi/o protein. The downstream signal transduction of GABAB is not very clear. MAPKs are serine-threonine kinases that, when activated, phosphorylate specific substrates such as phospolipases, transcription factors, and cytoskeletal proteins. Through this pathway, these proteins control physiological processes such as gene expression, mitosis, proliferation, motility, metabolism, and programmed cell death.In this study, we study on the ERK/MAPKs signal pathway induced by GABAB receptor in cerebellar granule neurons (CGN). We incubate the CGN cells with GABA and baclofen which is the agonist of GABAB receptor. We found that activation of GABAB receptor can rapidly stimulate ERK1/2 activation in a PTX-sensitive manner. The activation was blocked by pretreatment with the antagonist of GABAB receptor CGP54626 and the MEK1/2 inhibitor U0126. We also found that CGP7930 which is the agonist of GB2 can stimulate the ERK1/2 activation in a PTX-sensitive manner. We also found both baclofen and CGP7930 can rapidly stimulate CREB, that is dependent on the activation of ERK1/2.In a brief, our study has confirmed that the activation of GABAB receptor can induce the activation of ERK1/2 in CGN. The activation of ERK1/2 can stimulate the phosphorylation of CREB. We also found the CGP7930 can induce the activation of ERK1/2 and CREB. Given the crucial role of GABAB receptors in the signal transduction, it is important to understand their functional modulation.