Inhibitory influences of MIF-1 (PLG) and Tyr-MIF-1 (YPLG) on aggression and defeat-induced analgesia in mice

The effects of prolyl-leucyl-glycinamide (MIF-1, PLG), tyrosine-prolyl-leucyl-glycinamide (Tyr-MIF-1, YPLG) and the exogenous opiate antagonist, naloxone, on aggressive interactions and defeat-induced analgesia were examined in male mice. All three substances reduced the number of bites required to obtain defeat in subordinate mice during aggressive encounters, as well as blocking subsequent defeat-induced analgesia. Tyr-MIF-1 had significantly greater inhibitory effects than MIF. These results suggest that both MIF and Tyr-MIF-1 may function as endogenous opioid antagonists and have inhibitory influences on aggression, with the antagonistic effects of Tyr-MIF-1 being more potent than those of MIF-1.     

Pharmacological activities of the MIF-1 analogues Pro-Leu-Gly, Tyr-Pro-Leu-Gly and pareptide

The pharmacological activities of the related free acid analogues of MIF-1, Pro-Leu-Gly (PLG) and Tyr-Pro-Leu-Gly (YPLG), were investigated because of the possibility that they may be formed during the digestion of milk and wheat proteins in vivo. The amino acid sequences-Tyr-Pro-Leu-Gly- and -Pro-Leu-Gly- are present in proteins from these foods. Chronic administration of either PLG (0.25 mg/kg, SC, BID) or the control substance, pareptide (0.25 mg/kg, SC, BID), antagonized the development of tolerance to the cataleptic effects of haloperidol in mice. The effect of YPLG (0.25 mg/kg, SC, BID) on the development of this tolerance was borderline and not statistically significant. Nanomolar concentrations of PLG, YPLG, and pareptide each increased the in vitro binding of ³H-apomorphine to rat striatal receptors. In this in vitro system, bell-shaped dose response curves were observed for each peptide. The effects of these peptides on tolerance development and apomorphine binding are similar to those previously reported for MIF-1 and demonstrate that amidation at the carboxyl terminus is not required for biological activity.