Molecular Mechanisms And Function Of Gababr Research In The Neural Stem Cell C17.2

Gamma-aminobutyric acid type B receptors (GABABR) are G-protein-coupled receptors for the main inhibitory neurotransimitter in the brain.The metabotropic GABABR in GPCR family is very special, among G-protein coupled receptors,GABAB receptors are unique in that require GABAB1 and GABAB2 subunits assemble to form functional receptor and GABAB2 determine their subcellular localization.GABABR are implicated in a variety of physiological function,including neurological and psychiatric disorders and so on.We found that receptor agonist baclofen inhibits neural stem cells c17.2 proliferation.Western blotting exhibit that GABAB receptor activation phoshorylate extracellular regulated protein kinases (ERK),while lead to Src phosphorylation.These proteins phosphorylation will regulate a variety of physiological functions in neural stem cells,including inhibiting neual stem cells proliferation.In addition,we also noted that GABAB receptor activation transactivate IGF receptors and protect neural stem cells from apoptosis. I also showed that CGP7930,a positive allosteric regulator specific for GABAB2,alone could lead to ERK1/2 phosphorylation.CGP54626, GABAB receptor antagonist,could block effects of the agonist baclofen–induced Src/ERK1/2 / IGFR phosphorylation. AMPK inhibitor compound C can block agonist Metformin-induced cell inhibitory effect. GABAB receptor inhibitor CGP54626 could block the AMPK agonist Metformin-induced cell inhibitory effect.Taken together,GABABR regulate a series of signal pathway.This thesis is only a preliminary investigation for GABAB receptors of molecular mechanism in neural stem cells.