| Literature DB >> 10587082 |
K Lingenhoehl1, R Brom, J Heid, P Beck, W Froestl, K Kaupmann, B Bettler, J Mosbacher.
Abstract
Gamma-hydroxybutyrate (GHB) is a neuromodulator with high affinity binding sites in the mammalian brain. However, the receptor for GHB has not yet been identified. There are indications that GHB and gamma-aminobutyric acid (GABA) mediate their effects via the same receptor. We tested this hypothesis using GABA(B)R1/R2 receptors co-expressed with Kir3 channels in Xenopus oocytes. GHB activated these receptors with an EC50 of approximately 5 mM and a maximal stimulation of 69% when compared to the GABA(B) receptor agonist L-baclofen. GHB and L-baclofen did not amplify each others effect nor did they stimulate the GABA(B) receptor in a linearly additive manner. CGP54626A, 2-OH saclofen and CGP35348, three competitive GABA(B) receptor antagonists, inhibited the GHB induced response completely. A concentration of 30 mM GHB displaced [125I]CGP64213 binding at GABA(B)R1 expressed in COS cells by 21%. These results indicate that GHB is a weak partial agonist at the GABA binding site of GABA(B)R1/R2.Entities:
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Year: 1999 PMID： 10587082 DOI： 10.1016/s0028-3908(99)00131-8
Source DB: PubMed Journal: Neuropharmacology ISSN： 0028-3908 Impact factor: 5.250