Effects of bromohomoibotenate on metabotropic glutamate receptors.
(S)-Bromohomoibotenic acid [(S)-BrHIbo] stereoselectively antagonized glutamate-stimulated phosphoinositide (PI) hydrolysis in baby hamster kidney (BHK) cells expressing mGluR1a in a competitive manner with an IC50 of 250 microM. However, (S)-BrHIbo did not inhibit (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced PI hydrolysis in rat hippocampal slices (S)- or (R)-BrHIbo did not show any effects on forskolin-stimulated cAMP-formation in BHK cells expressing mGluR2 or mGluR4 but did displace [3H]2-amino-4-phosphonobutyrate ([3H]AP4) binding from rat corticalmembranes with high affinities (IC50 = 1.0 microM and 1.1 microM, respectively). These data suggest that (S)-BrHIbo may interest with multiple PI-coupled glutamate receptors, however, at concentrations that are several fold higher than for displacement of [3H]AP4 binding from rat cortical membranes.
Thomsen
C
C
Department of Receptor Neurochemistry, Novo Nordisk A/S, Måløv, Denmark.
Bau
A
A
Faarup
P
P
Foged
C
C
Kanstrup
A
A
Suzdak
P D
PD
D000613:Aminobutyrates / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*; D013237:Stereoisomerism
D000613:Aminobutyrates; D010716:Phosphatidylinositols; D011810:Quinoxalines; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C023366:4-bromohomoibotenic acid; D007051:Ibotenic Acid; D018698:Glutamic Acid; D000242:Cyclic AMP; C012729:2-amino-4-phosphonobutyric acid