MET-ENKEPHALIN-ARG-PHE AND PHE-MET-ARG-PHE-NH2 IN THE BRAIN AND SPINAL CORD

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Previously, we have presented several lines of evidence suggesting that Phe-Met-Arg-Phe-NH2-like (FMRF-NH2-like) peptide(s) in mammalian CNS may have modulatory role in opiate antinociception. FMRF-NH2 was a neuropeptide of clam origin, however, presence of FMRF-NH2-like peptides, which are distinct from the tetrapeptide FMRF-NH2, in mammalian CNS is now well known. In order to further explore the possible role of endogenous FMRF-NH2-like immunoreactivity in opiate antinociception, we have decided to chemically characterize the mammalian FMRF-NH2 like peptides. Two novel peptides, which are immunoreactive to FMRF-NH2 antiserum, have been purified to homogeneity from bovine brain and their amino acids sequences determined. Furthermore, these two peptides (octapeptide and octadecapeptide) were synthesized and biological activities were tested in rats. Both peptides, when injected intraventricularly, were found to decrease tail flick latencies of rats. One of the peptides, octapeptide, was found to attenuate the analgesia induced by morphine significantly. The molecular mechanism underlying this antiopiate effect of the novel mammalian FMRF-NH2 like peptide is under current investigation.