Comparative study on analgesic effect of Met⁵-enkephalin and related lipotropin fragments

Abstract

HUGHES et al.¹ have reported the isolation and structure of two pentapeptides from porcine brain with opiate agonist activity in isolated systems. The structure of one of these peptides, Met⁵-enkephalin, is identical with the sequence of pituitary β-lipotropin (β-LPH) between residues 61–65 (refs 2–4). To prove the biological correlation of brain enkephalin and pituitary β-LPH, a series of lipotropin fragments, LPH-(61–69)-⁵, LPH-(61–76)-⁶ and LPH-(61–91)-peptides^7–10, have been isolated and shown to have opiate agonist activity in vitro. Only few and controversial data have been available so far on the analgesic effect in vivo of the above or similar lipotropin fragments. Enkephalins have recently been reported to induce analgesia in vivo^11,12. Our preliminary data^5,13, however, seemed to contradict these observations, rather suggesting that some larger fragment(s) of β-LPH may have analgesic properties. We have therefore compared the analgesic effects of Met⁵-enkephalin and some lipotropin fragments containing the complete structure of Met⁵-enkephalin at their NH₂-terminus. The results show that the in vivo effect is a function of the length of the peptide chain, Met⁵-enkephalin being the least and LPH-(61–91)-peptide the most potent. During the preparation of this paper we have become aware of the recent observation of Bradbury and coworkers^10,14 on a strong analgesic activity of LPH-(61–91)-peptide.