| Tissue Specificity | Ubiquitously expressed in tissues including the forebrain, cerebellum, eye, atrium, ventricle, lung, stomach, small intestine, colon, liver, spleen, kidney, urinary bladder and skeletal muscle. Expressed at low levels in testis, and more highly in brain regions. Expression is high the brain regions including cerebral cortical layers, with higher expression in VIb than in the II-V layers, pyramidal CA1-CA3 cell layers and granular cell layers of the hippocampus, granular cell layers of the dentate gyrus, including the caudate, putamen, nucleus accumbens and olfactory tubercle, the granular layer cell layers of the medial habenula, in the cerebellum, predominantly in Purkinje cells, and in the granule cell layer. Also expressed in areas of the brain including the medial geniculate nucleus, substantia nigra, pars compacta, the ventral tegmental area, and in several thalamic, amygdaloid and hypothalamic nuclei, such as the arcuate nucleus of the hypothalamus and mammilary bodies of the hypothalamus. Expressed in the amacrine cell of the retina. Isoform 1A: Expressed in the brain, spinal cord, stomach, testis, adrenal gland, pituitary, spleen and prostate. Isoform 1B: Expressed in the brain, spinal cord, stomach, testis, kidney and liver. Expressed in Isoform 1C: Ubiquitously expressed. Isoform 1D: Expressed in the forebrain, cerebellum, eye, kidney and urinary bladder. Isoform 1E: Ubiquitously expressed with high expression the pyramidal CA1-CA3 cell layers of the hippocampus, the granule cell layers of the dentate gyrus and olfactory tubercle, the whole cortex, and Purkinje cells of the cerebellum. Moderate expression in the granule cell layer of the cerebellum. |
| Function | Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. |
