PHE-MET-ARG-PHE-NH2 LIKE PEPTIDES IN CNS--FUNCTION AND DISTRIBUTION

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The neuropeptide FLFQPQRF-NH(F-8-F-NH2) was originally isolated from the bovine brain and found to have morphine modulating activity. F-8-F-NH2 is highly localized in nerve terminals in posterior pituitary. The source of this pituitary F-8-F-NH2 was studied by various lesions. Our results suggest that at least part of the pituitary F-8-F-NH2 originates from supraoptic nuclei where it may be co-localized with Arg8-vasopressin. The role of F-8-F-NH2 in morphine tolerance and defeat-induced analgesia was studied using IgG from F-8-F-NH2 antiserum as antagonist. Injection (ICV) of IgG from F-8-F-NH2 antiserum restored the analgesic response to morphine in morphine-tolerant rats suggesting that endogenous F-8-F-NH2 contributes to morphine tolerance. Injection (ICV) of F-8-F-NH2 attenuated the defeat induced analgesia in the subordinate mice during the agonistic encounter. In contrast, ICV administration of IgG from F-8-F-NH2 antiserum augmented the levels of defeat induced analgesia. These results provide further evidence that F-8-F-NH2 may have a modulatory role in endogenous opioid mediated analgesia. Development of F-8-F-NH2 was studied in the rat CNS. F-8-F-NH2 was not detected in the brain or the spinal cord before the 18th embryonic day. The first F-8-F-NH2 positive fibers and terminals were detected in the median eminence on the 20th embryonic day. Postnatally, F- 8-F-NH2 system developed rapidly both in the brain and spinal cord, and was adult like by the age of 4 weeks. The late appearance of F-8-F-NH2 system during the ontogeny suggests that these peptides are expressed in relatively mature neurons. These results further imply that F-8-F-NH2 may not have a general function in the development of the nervous system, but rather may act as a neuromodulator or neurotransmitter since its production starts in neurons.