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

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We have previously isolated and chemically characterized two putative endogenous opiate antagonist peptides. In this study, antibodies against these two peptides were produced and distribution of these two peptides in brain and spinal cord was investigated by radioimmunoassay and also immunohistochemical technique. The immunohistochemical study was carried out with the cooperation of Dr. Pertti Panula at the University of Helsinki, Finland. These two peptides were found to be unevenly distributed in the brain with the highest concentrations in dorsal spinal cord and periaqueductal gray area and the lowest levels in cortex and cerebellum. In the spinal cord, immunoreactivities were found in laminae I-II of the posterior horn. Immunohistochemically, several groups of neurons in the rat brain were immunoreactive; immunoreactive cells were found in the cerebral cortex, lateral septal nucleus of the diagonal band, neostriatum, periventricular hypothalamic areas and several medullary nuclei. The identification of the two putative endogenous opiate antagonist peptides in brain neurons suggest that these two peptides may have functions in neurotransmission. The enrichment of these two peptides in dorsal spinal cord and periaqueductal gray area together with our past findings led us to suggest that these two peptides may participate in pain modulation. The proposed courses of the study on the two putative endogenous opiate antagonist peptides are: (1) to investigate the mechanism underlying the antiopiate action (2) to determine the distribution of receptors and (3) to explore the possible role of these peptides in development of opioid tolerance.