The Preliminary Study Of GABA_B Receptor-Mediated JNK Pathway Activation Molecular Mechanism And Function

Gamma-aminobutyric acid (GABA) type B receptor is a type of metabotropicreceptors and belongs to the G-protein coupled receptors (GPCRs) family C. GABA_BR iswidely distributed in the mammalian central neural system where it mediates slow andprolonged inhibition of synaptic transmission. However, in recent years, GABA_Breceptorhas been found exist in various tissues besides the central neural system. Studies haveshown that GABA_Breceptor activation can trans-activates IGF-1R which mediates thePI3K/AKT downstream signaling pathways such as PI3K/AKT, ERK activation,PI3K/AKT, ERK signals can regulate cell survival.In our research, the effect of GABA_Breceptor activation mediated JNK signalingpathway was investigated in cerebellar granule neurons (CGNs) and human embryonickidney293(HEK293). First I incubated the CGN cells with GABA which is the ligand ofGABA_Breceptor and Baclofen which is the agonist of GABA_Breceptor. I detected theactivation of JNK by Western Blot. I pretreated the CGN cells with CGP54626which isthe inhibitor of GABA_Breceptor, it down-regulated the level of JNK activation.Then Itransfected GB1and GB2plasmids into human embryonic kidney cells (HEK293),we alsodetected the activation of JNK. We found that GABA_Breceptor activation can regulate cellsurvival via JNK in a Gi/o-independent manner. Further research showed that smallGTPase Rac involved in the JNK signaling pathway.In summary, this study confirmed that GABA_Breceptor activation can regulate cellsurvival via JNK signaling pathway. To a certain extent, this result provides a basis forfurther study of the precise molecular mechanism and physiological function of JNKsignaling pathway which mediated by GABA_B receptor. This research not only enrichesthe physiological functions of membrane protein GABA_B receptor in neurons, but alsohas great significance in revealing the function of GABA_B receptor in nervous system.