Linked Life Data

10692480

Source:http://linkedlifedata.com/resource/pubmed/id/10692480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-4-10
pubmed:abstractText
The gamma-aminobutyric acid (GABA) receptor type B (GABA(B)R) is constituted of at least two homologous proteins, GABA(B)R1 and GABA(B)R2. These proteins share sequence and structural similarity with metabotropic glutamate and Ca(2+)-sensing receptors, both of which are sensitive to Ca(2+). Using rat brain membranes, we report here that the affinity of GABA and 3-aminopropylphosphinic acid for the GABA(B)R receptor is decreased by a factor >10 in the absence of Ca(2+). Such a large effect of Ca(2+) is not observed with baclofen or the antagonists CGP64213 and CGP56999A. In contrast to baclofen, the potency of GABA in stimulating GTPgammaS binding in rat brain membranes is also decreased by a factor >10 upon Ca(2+) removal. The potency for Ca(2+) in regulating GABA affinity was 37 microM. In cells expressing GABA(B)R1, the potency of GABA, but not of baclofen, in displacing bound (125)I-CGP64213 was similarly decreased in the absence of Ca(2+). To identify residues that are responsible for the Ca(2+) effect, the pharmacological profile and the Ca(2+) sensitivity of a series of GABA(B)R1 mutants were examined. The mutation of Ser269 into Ala was found to decrease the affinity of GABA, but not of baclofen, and the GABA affinity was found not to be affected upon Ca(2+) removal. Finally, the effect of Ca(2+) on the GABA(B) receptor function is no longer observed in cells coexpressing this GABA(B)R1-S269A mutant and the wild-type GABA(B)R2. Taken together, these results show that Ser269, which is conserved in the GABA(B)R1 protein from Caenorhabditis elegans to mammals, is critical for the Ca(2+)-effect on the heteromeric GABA(B) receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
419-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10692480-Amino Acid Sequence, pubmed-meshheading:10692480-Animals, pubmed-meshheading:10692480-Calcium, pubmed-meshheading:10692480-Cells, Cultured, pubmed-meshheading:10692480-Dimerization, pubmed-meshheading:10692480-Humans, pubmed-meshheading:10692480-Molecular Sequence Data, pubmed-meshheading:10692480-Mutagenesis, Site-Directed, pubmed-meshheading:10692480-Point Mutation, pubmed-meshheading:10692480-Rats, pubmed-meshheading:10692480-Receptors, Calcium-Sensing, pubmed-meshheading:10692480-Receptors, Cell Surface, pubmed-meshheading:10692480-Receptors, GABA-B, pubmed-meshheading:10692480-Receptors, Metabotropic Glutamate, pubmed-meshheading:10692480-Recombinant Proteins, pubmed-meshheading:10692480-Sequence Homology, Amino Acid, pubmed-meshheading:10692480-Serine, pubmed-meshheading:10692480-gamma-Aminobutyric Acid
pubmed:year
2000
pubmed:articleTitle
Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit.
pubmed:affiliation
Centre Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique de Pharmacologie-Endocrinologie, UPR 9023-Centre National de la Recherche Scientifique, Montpellier, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't