GPCR family 3, gamma-aminobutyric acid receptor, type B1 (IPR002456)
Short name: GPCR_3_GABA_rcpt_B1
Overlapping homologous superfamilies
- Periplasmic binding protein-like I (IPR028082)
- GPCR family 3, GABA-B receptor (IPR002455)
- GPCR family 3, gamma-aminobutyric acid receptor, type B1 (IPR002456)
GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length [PMID: 17266540]. Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors [PMID: 1309649, PMID: 8255296, PMID: 10773016, PMID: 9292726]. As these receptors regulate many important physiological processes they are potentially promising targets for drug development.
GABA is the principal inhibitory neurotransmitter in the brain, and signals through ionotropic (type A and type C) and metabotropic (type B) receptor systems. The type B receptors have been cloned, and photoaffinity labelling experiments suggest that they correspond to two highly conserved receptor forms in the vertebrate nervous system [PMID: 9069281]. These receptors are involved in the fine tuning of inhibitory synaptic transmission [PMID: 9844003]. Presynaptic receptors inhibit neurotransmitter release by down-regulating high-voltage activated calcium channels, while postsynaptic receptors decrease neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials [PMID: 9844003]. The type B receptors negatively couple to adenylyl cyclase and show sequence similarity to the metabotropic receptors for the excitatory neurotransmitter L-glutamate. The physiological form of the B receptor may be a heterodimer of the B1 and B2 subtypes [PMID: 9872316].
Neurophysiological and pharmacological studies point to a major role of the GABA type B receptor in the epileptogenesis of absence seizures [PMID: 9933300]. Using in situ hybridisation, the gene encoding the human GABA type B1 receptor has been mapped to chromosome 6p21.3, in the vicinity of a susceptibility locus (EJM1) for idiopathic generalised epilepsies, identifying a candidate gene for inherited forms of epilepsy [PMID: 9844003, PMID: 9933300].
The metabotropic glutamate receptor-like protein E from Dictyostelium discoideum, which is probably a receptor for GABA and glutamate, is also included in this entry [PMID: 16672332].
- cd15291 (7tmC_GABA-B-R1)