Up-regulation of GABA(B) receptors by chronic administration of the GABA(B) receptor antagonist SCH 50,911.
Chronic treatment of mice with the specific gamma-aminobutyric acid(B) (GABA(B)) receptor antagonist (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50,911) increased both the number of GABA(B) receptors in the whole brain (measured as [3H]CGP 54626 [S-(R,R)]-3-[[1-(3,4-dichlorophenyl)amino]-2-hydroxypropyl](cyclohexylmethyl)phosphinic acid hydrochloride binding) and the ability of baclofen to activate GABA(B) receptor coupled G-protein (measured as % reduction of the EC50 of baclofen to activate [35S]GTP(gamma)S binding). The results indicate that persistent blockade of GABA(B) receptors leads to their compensatory up-regulation and suggest that GABA(B) receptors are tonically activated by endogenous GABA.
Pibiri
Fabio
F
B.B. Brodie Department of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato (CA), Italy.
Carboni
Giovanni
G
Carai
Mauro A M
MA
Gessa
Gian Luigi
GL
Castelli
M Paola
MP
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D014316:Tritium; D015854:Up-Regulation
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D013462:Sulfur Radioisotopes; D014316:Tritium; C107353:CGP 54626; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001418:Baclofen