Regional differences in the metabolism of Tyr-MIF-1 and Tyr-W-MIF-1 by rat brain mitochondria.

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) are endogenous neuropeptides with opiate modulating and other CNS effects. After incubation of the tritiated tetrapeptides with fractions of tissue from different areas of rat brain, formation of the metabolites was determined by HPLC. Marked regional differences in degradation were found for both peptides. The metabolism of Tyr-MIF-1, resulting in the formation of the biologically active MIF-1 (Pro-Leu-Gly-NH2), was greater in the mitochondrial than in the synaptosomal fractions. In the mitochondrial fraction, about twice as much MIF-1 was formed in brain cortex than in striatum, diencephalon, or midbrain/pons medulla. These results, showing differential metabolism in various areas of the brain, indicate another means for regulation of the concentrations of neuropeptides.