F
IPR002456

GPCR family 3, gamma-aminobutyric acid receptor, type B1

InterPro entry
Short nameGPCR_3_GABA_rcpt_B1
family relationships

Description

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
[5]
. 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
[2, 6, 3, 4]
. 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
[7]
. These receptors are involved in the fine tuning of inhibitory synaptic transmission
[8]
. 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
[8]
. 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
[9]
.

Neurophysiological and pharmacological studies point to a major role of the GABA type B receptor in the epileptogenesis of absence seizures
[1]
. 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
[8, 1]
.

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
[10]
.

References

1.Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy. Peters HC, Kammer G, Volz A, Kaupmann K, Ziegler A, Bettler B, Epplen JT, Sander T, Riess O. Neurogenetics 2, 47-54, (1998). View articlePMID: 9933300

2.A family of metabotropic glutamate receptors. Tanabe Y, Masu M, Ishii T, Shigemoto R, Nakanishi S. Neuron 8, 169-79, (1992). View articlePMID: 1309649

3.Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor. Sullivan R, Chateauneuf A, Coulombe N, Kolakowski LF Jr, Johnson MP, Hebert TE, Ethier N, Belley M, Metters K, Abramovitz M, O'Neill GP, Ng GY. J. Pharmacol. Exp. Ther. 293, 460-7, (2000). View articlePMID: 10773016

4.A new multigene family of putative pheromone receptors. Ryba NJ, Tirindelli R. Neuron 19, 371-9, (1997). View articlePMID: 9292726

5.Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors. Brauner-Osborne H, Wellendorph P, Jensen AA. 8, 169-84, (2007). View articlePMID: 17266540

6.Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC. Nature 366, 575-80, (1993). View articlePMID: 8255296

7.Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B. Nature 386, 239-46, (1997). View articlePMID: 9069281

8.Human gamma-aminobutyric acid type B receptors are differentially expressed and regulate inwardly rectifying K+ channels. Kaupmann K, Schuler V, Mosbacher J, Bischoff S, Bittiger H, Heid J, Froestl W, Leonhard S, Pfaff T, Karschin A, Bettler B. Proc. Natl. Acad. Sci. U.S.A. 95, 14991-6, (1998). View articlePMID: 9844003

9.Heterodimerization is required for the formation of a functional GABA(B) receptor. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH. Nature 396, 679-82, (1998). View articlePMID: 9872316

10.GABA induces terminal differentiation of Dictyostelium through a GABAB receptor. Anjard C, Loomis WF. Development 133, 2253-61, (2006). View articlePMID: 16672332

GO terms

Cross References

  • IUPHAR receptor code
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