Panther Pathway: P05731 GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system. It mediates its action through the ionotropic GABA-A and GABA-B receptors. GABA-A receptors form ion channels, while GABA-B receptors are G-protein coupled receptors. This pathway focuses on signaling pathway mediated by GABA-B receptor. GABA-B receptor are located on both presynaptic and postsynaptic membrane. Presynaptic GABA-B receptors are subdivided into autoreceptors that control GABA release, and heteroreceptors that inhibits all other neurotransmitter release. Upon binding to GABA, the presynaptic GABA-B receptor decreases Ca ion influx by inhibiting voltage-dependent Ca channels, particularly N-type and P/Q type, via beta and gamma subunit of G protein, thus lowering the presynaptic Ca concentration and decreasing neurotransmitter release. Postsynaptic GABA-B receptors induce a slow inhibitory postsynaptic current through the activation of an inward rectifying K channel (GIRK). In addition, recent studies found that synaptic plasticity can be controlled by the cAMP pathway. GABA-B receptors have been found to play a role in the field of substance abuse or addition. It has been reported that administration of GABA-B agonist, such as baclofen, can reduce patients' craving for cocaine or alcohol. Recently, an association study showed close linkage between several SNPs of GABA B2 receptor and nicotine dependency. Medline=11311380 Medline=16539894 OMIM=607340 PMID: 11311380 PMID: 16539894 4.0 Long Name: Gi/oalpha Synonym: Synonym not specified Accession: P05757 s33 PROTEIN pr2 Long Name: Gamma-aminobutyric acid B receptor Synonym: GABBR2,G protein-coupled receptor 51 Accession: P05756 s18 PROTEIN pr1 Long Name: Gamma-aminobutyric acid B receptor Synonym: GABBR2,G protein-coupled receptor 51 Accession: P05756 s33 PROTEIN pr1 Long Name: Gbeta Synonym: Synonym not specified Accession: P05755 s33 PROTEIN pr3 Long Name: Ggamma Synonym: Synonym not specified Accession: P05754 s33 PROTEIN pr4 Long Name: Gi/oalpha Synonym: Synonym not specified Accession: P05757 s18 PROTEIN pr2 Long Name: Gbeta Synonym: Synonym not specified Accession: P05755 s18 PROTEIN pr3 Long Name: Ggamma Synonym: Synonym not specified Accession: P05754 s18 PROTEIN pr4 Long Name: Gbeta Synonym: Synonym not specified Accession: P05755 s27 PROTEIN pr3 Long Name: Ggamma Synonym: Synonym not specified Accession: P05754 s27 PROTEIN pr4 Long Name: Gamma-aminobutyric acid B receptor Synonym: GABBR2,G protein-coupled receptor 51 Accession: P05756 s28 PROTEIN pr1 Long Name: GABA Synonym: Synonym not specified Accession: S05809 s33 SIMPLE_MOLECULE GABA Long Name: GABA Synonym: Synonym not specified Accession: S05809 s28 SIMPLE_MOLECULE GABA Long Name: N-ethylmaleimide-sensitive factor attachment protein receptor Synonym: SNARE Accession: P05759 s53 PROTEIN p10 Long Name: Ca2+ Synonym: Synonym not specified Accession: U05899 s53 ION Ca_super_2+ Long Name: Gamma-aminobutyric acid B receptor Synonym: GABBR2,G protein-coupled receptor 51 Accession: P05756 s65 PROTEIN pr1 Long Name: Gi/oalpha Synonym: Synonym not specified Accession: P05757 s65 PROTEIN pr2 Long Name: Gbeta Synonym: Synonym not specified Accession: P05755 s65 PROTEIN pr3 Long Name: Ggamma Synonym: Synonym not specified Accession: P05754 s65 PROTEIN pr4 Long Name: Gamma-aminobutyric acid B receptor Synonym: GABBR2,G protein-coupled receptor 51 Accession: P05756 s70 PROTEIN pr1 Long Name: GABA Synonym: Synonym not specified Accession: S05809 s70 SIMPLE_MOLECULE GABA Long Name: Ggamma Synonym: Synonym not specified Accession: P05754 s70 PROTEIN pr4 Long Name: Gbeta Synonym: Synonym not specified Accession: P05755 s70 PROTEIN pr3 Long Name: Gi/oalpha Synonym: Synonym not specified Accession: P05757 s70 PROTEIN pr2 Long Name: GABA Synonym: Synonym not specified Accession: S05809 s77 SIMPLE_MOLECULE GABA Long Name: Gamma-aminobutyric acid B receptor Synonym: GABBR2,G protein-coupled receptor 51 Accession: P05756 s77 PROTEIN pr1 Long Name: Gbeta Synonym: Synonym not specified Accession: P05755 s80 PROTEIN pr3 Long Name: Ggamma Synonym: Synonym not specified Accession: P05754 s80 PROTEIN pr4 SQUARE_CLOSEUP_SOUTHEAST SQUARE_CLOSEUP_NORTHEAST OVAL inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive active inactive active inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive SRI International Presynaptic Postsynaptic Synaptic vesicle Long Name: GABA Synonym: Synonym not specified Accession: S05809 inside SIMPLE_MOLECULE GABA Long Name: GABA-B receptor/ G protein complex Synonym: Synonym not specified Accession: U05887 transmembrane COMPLEX GABA_minus_B receptor_slash__br_G protein_br_complex Long Name: Gi/oalpha Synonym: Synonym not specified Accession: P05757 inside PROTEIN pr2 Long Name: Gbetagamma complex Synonym: Synonym not specified Accession: U05888 inside COMPLEX G_beta__gamma_ complex Long Name: GABA-B receptor/ GABA complex Synonym: Synonym not specified Accession: U05889 transmembrane COMPLEX GABA_minus_B_br_receptor_slash__br_GABA complex Long Name: GABA-B receptor/ GABA/ G protein complex Synonym: Synonym not specified Accession: U05890 transmembrane COMPLEX GABA_minus_B_br_receptor_slash__br_GABA_slash__br_G protein complex Long Name: Voltage-dependent Ca channel Synonym: Synonym not specified Accession: P05753 transmembrane PROTEIN pr5 Long Name: Ca2+ Synonym: Synonym not specified Accession: U05899 inside ION Ca_super_2_plus_ Long Name: Ca2+ Synonym: Synonym not specified Accession: U05899 inside ION Ca_super_2_plus_ Long Name: Adenylate cyclase Synonym: adenylyl cyclase,adenyl cyclase Accession: P05760 inside PROTEIN pr6 Long Name: cAMP-dependent protein kinase Synonym: Synonym not specified Accession: P05752 inside PROTEIN pr7 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05891 transmembrane COMPLEX Complex_br_(SNARE Complex/Ca_super_2+) Long Name: N-ethylmaleimide-sensitive factor attachment protein receptor Synonym: SNARE Accession: P05759 transmembrane PROTEIN p10 Long Name: Glutamate Synonym: Synonym not specified Accession: S05810 inside SIMPLE_MOLECULE Neurotransmitter Long Name: Glutamate Synonym: Synonym not specified Accession: S05810 inside SIMPLE_MOLECULE Neurotransmitter Long Name: GABA-B receptor/ G protein complex Synonym: Synonym not specified Accession: U05892 transmembrane COMPLEX GABA_minus_B receptor_slash__br_G protein_br_complex Long Name: GABA-B receptor/ GABA/ G protein complex Synonym: Synonym not specified Accession: U05893 transmembrane COMPLEX GABA_minus_B_br_receptor_slash__br_GABA_slash__br_G protein complex Long Name: GABA-B receptor/ GABA complex Synonym: Synonym not specified Accession: U05894 transmembrane COMPLEX GABA_minus_B_br_receptor_slash__br_GABA complex Long Name: Gbetagamma complex Synonym: Synonym not specified Accession: U05895 inside COMPLEX G_beta__gamma_ complex Long Name: Gi/oalpha Synonym: Synonym not specified Accession: P05757 inside PROTEIN pr2 Long Name: Inwardly rectifying potassium channel Kir3.1 Synonym: GIRK1,KCNJ3 Accession: P05758 transmembrane PROTEIN pr8 Long Name: K+ Synonym: Synonym not specified Accession: U05898 inside ION K_super__plus_ Long Name: K+ Synonym: Synonym not specified Accession: U05898 inside ION K_super__plus_ Long Name: Modulate neuronal function Synonym: Synonym not specified Accession: U05896 inside PHENOTYPE neuronal function Long Name: Target ion channel modulation Synonym: Synonym not specified Accession: U05900 inside PHENOTYPE Target ion channel HETERODIMER_ASSOCIATION 0.19563966235474517,0.3537190309142725 csa2 sa3 csa1 DISSOCIATION 0.5284018987341765,0.23557489451477043 csa1 csa4 sa12 csa3 STATE_TRANSITION sa20 sa21 csa3 TRANSPORT 0.3176527492136376,-0.0020649304497126764 sa22 sa23 sa21 STATE_TRANSITION sa24 sa25 sa12 STATE_TRANSITION sa26 sa27 sa25 HETERODIMER_ASSOCIATION 0.39237025780758783,0.6142505406705725 sa34 sa23 csa6 TRANSPORT 0.5573596130736447,3.769359545358064E-4 sa46 sa37 csa6 HETERODIMER_ASSOCIATION 0.32777319800093174,0.36103096501622867 csa8 sa47 csa9 DISSOCIATION 0.4653678576088214,0.12964800483426764 csa9 csa10 csa11 sa61 STATE_TRANSITION sa62 sa63 csa11 TRANSPORT 0.3209306907932552,1.7763568394002505E-15 sa64 sa65 sa63 MODULATION sa27 sa28 MODULATION sa27 sa29