Tyr-MIF-1 augments benzodiazepine receptor binding in vivo.
Behavioral and limited neurochemical evidence indicates possible links between the endogenous opiate and gamma-aminobutyric acid (GABA)-benzodiazepine receptor systems. A previous study using in vitro techniques indicated that MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), peptides with anti-opiate activity, enhanced GABA-stimulated benzodiazepine binding. To assess the activity of these peptides under in vivo conditions, we evaluated their effects on benzodiazepine receptor binding as determined by specific uptake of the benzodiazepine antagonist [3H]-Ro15-1788. Tyr-MIF-1, at a dose of 1 mg/kg IP, significantly augmented benzodiazepine binding in cortex and hippocampus but not in cerebellum, hypothalamus, or pons-medulla. Increases in binding were due in large part to increased apparent affinity at the receptor. At none of the doses of MIF-1 (0.1, 1 and 10 mg/kg) or at the highest (10 mg/kg) and lowest (0.1 mg/kg) doses of Tyr-MIF-1 was there any significant alteration in benzodiazepine binding in any region evaluated. These results indicate that peptide-benzodiazepine receptor interactions may also occur in vivo.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000378:metabolism*
D011963:Receptors, GABA-A; D002998:Clonazepam; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone