Allosteric modulation of t-[35S]butylbicyclophosphorothionate binding in rat brain by melatonin.
In order to clarify melatonin's pharmacological interaction with central gamma-aminobutyric acid (GABA) receptors, its effects on the binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS), which specifically labels GABA-gated chloride channels, was examined in the rat brain. Saturation binding studies indicated that the effect of melatonin (500 microM) was due to a significant decrease in binding site density (Bmax) while the dissociation constant (Kd) was unchanged. The central-type benzodiazepine (BZ) receptor site antagonist Ro15-1788 (flumazenil) did not reverse the effect of melatonin but blocked the effect of diazepam, indicating that central-type BZ sites do not mediate the effects of melatonin. Since the ability to allosterically inhibit TBPS binding is characteristic of GABA-positive ligands, these findings provide further evidence that the pharmacological effects of melatonin involve enhancement of central GABAergic activity.
Niles
L P
LP
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario.
Peace
C H
CH
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011963:Receptors, GABA-A; C037476:tert-butylbicyclophosphorothionate; D008550:Melatonin