Extreme stability of Tyr-MIF-1 in CSF

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), an endogenous brain peptide, was incubated at 37 degrees C in cerebrospinal fluid (CSF) from rats and the amount remaining in intact from determined by high performance liquid chromatography (HPLC). By 3 min, a time at which Tyr-MIF-1 had been considerably degraded by rat plasma, essentially no degradation of the tetrapeptide had occurred in CSF. Tyr-MIF-1 persisted in mainly intact form for the 8 days tested, with a calculated half-time degradation of 11.4 days. The simultaneous addition to CSF of equal amounts of Tyr-MIF-1 tritiated on the Tyr and Tyr-MIF-1 tritiated on the Pro facilitated determination of whether Tyr-MIF-1 serves as a precursor of MIF-1 (Pro-Leu-Gly-NH2) in CSF. This possibility was excluded by the findings that the primary metabolite was Tyr-Pro, with minimal and equal amounts of the free amino acids Pro and Tyr being formed, but no MIF-1. The results show the extreme stability of Tyr-MIF-1 in CSF and are consistent with a role for this peptide in the CNS.