Study on the antinociceptive action of Tyr-K-MIF-1, a peptide from the MIF family.

1. Tyr-K-MIF-1 is a melanocyte inhibiting factor (MIF) neuropeptide, isolated from the brain. Opposite to other MIFs (Tyr-MIF-1, Tyr-W-MIF-1), it has a very low affinity for opiate mu-receptors, but interacts with Tyr-MIF-1 specific binding sites. Tyr-MIF-1 and Tyr-W-MIF-1 evoke antinociception mainly by activating opioid receptors. We investigated the possible antinociceptive effect of Tyr-K-MIF-1 and the involvement of histaminergic system in its mechanism of action. 2. Tested on rats by paw-pressure test, Tyr-K-MIF-1 (0.5, 1 and 2 mg kg(-1)) was associated with short-lasting analgesia, which was abolished by naloxone (1 mg kg(-1)). 3. Injected intraperitoneally (i.p.) 15 min before Tyr-K-MIF-1, antagonists of H(1) (diphenhydramine, 100 mg kg(-1)) or H(2) (famotidine, 0.3 and 0.6 mg kg(-1)) histamine receptors diminished peptide antinociceptive effect. Simultaneous H(1)- and H(2) blockade, as well as pretreatment with 5 mg kg(-1) dimaprit (H(2) agonist) abolished Tyr-K-MIF-1-induced analgesia. Tyr-K-MIF-1-induced analgesia was also abolished by treatment with R-(alpha)-methylhistamine (10 mg kg(-1), i.p.), an H(3) histamine receptor agonist that acts to inhibit histamine release. 4. Our results together with data reported in the literature support the conclusion that activation of the histaminergic system is involved in the mechanism of Tyr-K-MIF-1-induced antinociception.