Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors.
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.
Lingenhoehl
K
K
Nervous System Research, Novartis Pharma AG, Basel, Switzerland.
Brom
R
R
Heid
J
J
Beck
P
P
Froestl
W
W
Kaupmann
K
K
Bettler
B
B
Mosbacher
J
J
D018686:Anesthetics, Intravenous / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D018756:GABA Antagonists / Q000378:metabolism / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D012978:Sodium Oxybate / Q000378:metabolism / Q000494:pharmacology*; D014981:Xenopus
D018686:Anesthetics, Intravenous; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D012978:Sodium Oxybate