FMRF-AMIDE LIKE PEPTIDES IN CNS--FUNCTION AND DISTRIBUTION

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Neuropeptide, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2), was initially detected by the antisera raised against the molluscan cardioexcitatory peptide FMRF-NH2 and subsequently isolated from bovine brain. Accumulating evidence suggests that F-8-F-NH2 may have a role in modulating opiate effects. In this study, the functional role(s) of FMRF-NH2 immunoreactivity (IR) including F-8-F-NH2 was further investigated. I.C.V. infusion of IgG from F-8-F-NH2 antiserum (as a specific F-8-F-NH2, antagonist) significantly reduced the number of abstinence signs precipitated by naloxone in morphine-dependent rats. This result and the previous findings of other investigators, that F-8-F-NH, can precipitate withdrawal in morphine dependent rats, suggest that F-8-F-NH2 may be involved in abstinence syndrome. Studies on pituitary F-8-F-NH2-IR indicate that there may be an interaction between F-8-F-NH2 and Arg(8)- vasopressin. In Brattleboro and salt loaded rats, animals known to have modified AVP biosynthesis, secretions of F-8-F-NH2-IR from pituitaries were found to be increased. Furthermore, in the pituitary, the postnatal development of F-8-F-NH2 was found to be very similar to that of AVP. Mammalian FMRF-NH2-IR is composed of multiple molecular forms which are not identical to FMRF-NH2. In this study 3 additional FMRF-NH2-like peptides were purified from rat -spinal cords and determination of their 'structures is in progress. The proposed courses of this project are 1) to continue the study on the functional role of F-B-F-NH, in the pituitary and 2) to determine the structures and biological activities of the newly isolated FMRF-NH2-like peptides.