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

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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 -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 H1 (diphenhydramine, 100 mg kg−1) or H2 (famotidine, 0.3 and 0.6 mg kg−1) histamine receptors diminished peptide antinociceptive effect. Simultaneous H1- and H2 blockade, as well as pretreatment with 5 mg kg−1 dimaprit (H2 agonist) abolished Tyr-K-MIF-1-induced analgesia. Tyr-K-MIF-1-induced analgesia was also abolished by treatment with R-(α)-methylhistamine (10 mg kg−1, i.p.), an H3 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.

Keywords: MIFs; antinociception; histaminergic system; neuropeptides

Document Type: Research Article


Publication date: April 1, 2007


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