부산대학교 도서관

Mastoparan(MP), a tetradecapeptide from wasp venom, acts as a secretagogue and stimulates catecholamine(CA)release from adrenal chromaffin cells. On the relationship between the structure and CA releasing activity from chromaffin cells of MP or MP fragments, we have previously reported that the active site of MP for CA release was located on each side at the N-terminal or Cterminal, N-terminal tetrapeptide(INLK-NH_2;N-4)and C-terminal tetrapeptide(KKIL-NH_2;C-4)of MP had no CA releasing activity but inhibited ACh-or MP-stimulated CA release, MP fragments(N-4, C-4)inhibited nicotine-or carbamyl-choline-stimulated CA release but not histamine-, bradykinin-or angiotensin II-induced secretion, and MP fragments selectively inhibited nicotinic agonists-stimulated CA release by attacking the nicotinic acetylcholine receptor(nAChR)on the site(s)other than ACh. Further, it was reported that N-terminal three amino acid residues-substituted mastoparan T enhanced it's original CA releasing activity. In this study, we newly synthesized thirteen N-4 analogs and tested their inhibitory activities toward nAChR.It was shown that(1)hydro-phobic or basic amino acid-substituted N-4 enhanced it's original activity to inhibit nAChR, (2)LLLK-NH_2 had about six times as much as the inhibitory activity of N-4 and was the most potent inhibitory peptide of all the N-4 analogs. From the relationship between the structure and inhibitory activity of N-4 analogs toward nAChR, the site(s) on nAChR attacked by N-4 are suggested to be made up of hydrophobic amino acids and acidic amino acids. These newly synthesized peptides are expected to be a powerful medicine for the nAChR-related disease.