Synthesis of Neurokinin B Analogs and Their Activities as Agonists and Antagonists

抄録

Nine neurokinin B (NKB) related octapeptide analogs, substituted with Arg for His³, or Gly, D-Trp, D-Ala or D-Phe for Phe⁶, or Gly for Val⁷, or D-Trp or D-Ala for Gly⁸ in the original sequence, were synthesized by the solid-phase method. The biological activity of the synthetic analogs was assayed on isolated guinea-pig ileum and rat duodenum. None of the analogs possessed agonistic activity. In the guinea-pig ileum assay, [Arg³, Gly⁶, D-Ala⁸] - and [Arg³, Gly⁶, D-Trp⁸] -NKB (3-10) were found to act as fairly potent antagonists against NKB, but showed no antagonistic effect against substance P (SP) or neurokinin A (NKA). [Arg³, D-Ala⁶, D-Trp⁸] -and [Arg³, D-Trp^{6, 8}, Gly⁷] -NKB (3-10) showed antagonistic activities against NKB and SP, and NKB, SP and NKA, respectively, in the ileum assay, while the latter acted as an antagonist against NKB, but not against SP or NKA in the rat duodenum assay.