title: Tyr-MIF-1 binding in brain is not altered by ligands selective for the GABAA/benzodiazepine receptor.
abstract: Binding of benzodiazepines to the benzodiazepine gamma-aminobutyric acid (GABA) receptor-chloride channel complex has been shown to be altered by Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2). This raised the possibility of allosteric binding interactions between Tyr-MIF-1 sites and the GABAA receptor complex. We tested this possibility in rat brain by examining the binding of Tyr-MIF-1 to brain membranes in the presence of clonazepam, GABA, a combination of clonazepam and GABA, RO15788, or picrotoxinin. None of the tested substances affected Tyr-MIF-1 binding. We also tested mouse cortex for changes in Tyr-MIF-1 binding in the presence of ligands that bind to the GABA/benzodiazepine/chloride channel complex. Clonazepam, flunitrazepam, RO15788, and picrotoxinin at concentrations ranging from 10(-13) to 10(-5) M, each in the absence or presence of GABA at concentrations ranging from 10(-9) to 10(-5) M, each in the absence or presence of GABA at concentrations ranging from 10(-9) to 10(-6) M, did not significantly alter the binding of Tyr-MIF-1. The results indicate that simple bidirectional allosteric interactions between Tyr-MIF-1 binding sites and benzodiazepine, GABA or chloride channel binding sites are not likely to be the mechanism by which Tyr-MIF-1 affects binding at this complex.
authors.affiliation: Veterans Administration Medical Center, New Orleans, LA.
authors.forename: J E
authors.initials: JE
authors.lastname: Zadina
authors.forename: A J
authors.initials: AJ
authors.lastname: Kastin
authors.forename: L J
authors.initials: LJ
authors.lastname: Ge
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002998:Clonazepam / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; D002998:Clonazepam; D005445:Flunitrazepam; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone