Gamma-aminobutyric acid type B receptor subunit 1
- GABBR1
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. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.
Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
