PHE-MET-ARE-PHE-NH2 LIKE PEPTIDES IN THE BRAIN AND SPINAL CORD

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We have previously isolated from bovine brain and chemically characterized two putative endogenous opiate antagonist peptides. These peptides, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe- NH2 and Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala- Ala-Pro-Gln-Arg-Phe-NH2, were found to be highly localized in periaqueductal gray and dorsal spinal cord, areas important for opiate antinociception. In this study, distribution and pathways of these two peptides in rat spinal cord were studied in detail by radioimmunoassay and immunohistochemistry. Levels of these two peptides are highest in dorsal gray and lowest in ventral white. After spinal cord transection, levels of these two peptides decreased significantly caudal to the transected region indicating the presence of descending pathways of these two peptides. Immunohistochemically, intense immunoreactivity was observed in substantia gelatinosa of posterior horn, scattered fibers were found in deeper laminae of posterior horn. The morphological study further suggests the possible role of these two peptides in opiate mediated analgesia. In further studying the biological property of these two peptides, they were found to elevate mean arterial blood pressure. This pressor activity was attenuated by prior treatment with guanethidine or prazocin. The results suggest that these two peptides increase mean arterial pressure by potentiating the release of catecholamines. The proposed course of this study is to investigate the mechanism by which these two peptides act to modulate opiate analgesia including release of these two peptides from spinal cord and receptors for these two peptides.