Trans-gamma-hydroxycrotonic acid binding sites in brain: evidence for a subpopulation of gamma-hydroxybutyrate sites.
Trans-gamma-hydroxycrotonate (THCA), a compound naturally present in rat brain, possesses high-affinity binding sites with a heterogeneous distribution which are superimposable with those for gamma-hydroxybutyrate (GHB). Binding studies of THCA on rat brain membranes revealed two binding components, one of high affinity (Kd1, 7 nM, Bmax1 42 fmol/mg protein) and the other of low affinity (Kd2, 2 microM, Bmax2 13 pmol/mg protein). Displacement curves of [3H]THCA by THCA and GHB or of [3H]GHB by THCA are in favour of the existence of a specific high affinity site for THCA. Quantitative autoradiography with image analysis of [3H]THCA binding in rat brain slices indicated that [3H]THCA high affinity binding was displaced at a lower potency by GHB. THCA showed also some selectivity in displacing [3H]GHB from its high affinity binding site (Kd = 95 nM). This mutual overlap favours a subpopulation of GHB receptors, which have THCA as a natural ligand, showing partial agonistic properties compared to GHB. The functional significance of this result remains unknown.
Hechler
V
V
Centre de Neurochimie du CNRS, Strasbourg, France.
Schmitt
M
M
Bourguignon
J J
JJ
Maitre
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012978:Sodium Oxybate / Q000378:metabolism*
D006885:Hydroxybutyrates; D017981:Receptors, Neurotransmitter; C035142:4-hydroxy-2-butenoic acid; D012978:Sodium Oxybate