MIF-1 and Tyr-MIF-1 augment muscimol-stimulated chloride uptake in cerebral cortex

The peptides MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) recently have been found to augment the effects of gamma-aminobutyric acid (GABA) on benzodiazepine receptor binding and chloride channel binding (Tyr-MIF-1) at the GABAA receptor complex. To determine whether these peptides affect the function of this complex in chloride transport, we evaluated chloride uptake stimulated by the GABA analog muscimol in synaptoneurosome preparations. In mice treated with either MIF-1 or Tyr-MIF-1 (1 mg/kg IP), maximal chloride uptake in cortex was increased compared with controls. The two peptides had similar effects in cortical preparations, but in cerebellum neither peptide altered chloride uptake. No differences from controls were observed in cortical synaptoneurosomes treated in vitro with either MIF-1 or Tyr-MIF-1. These results suggest that the brain peptides MIF-1 and Tyr-MIF-1 alter function at the GABAA receptor complex, perhaps by binding at a specific peptide receptor.