Development of new mastoparan-related peptides which stimulate or inhibit the secretory activity of cells

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This study aimed to develop new mastoparan (MP)-related peptides which stimulate or inhibit the secretory activity of cells such as adrenal chromaffin cells and mast cells. We designed and synthesized 7 MP fragments including N-terminal four residues (INLK-NH_s ; N-4) and C-terminal four residues (KKIL-NH_2 ; C-4) and their several analogs (13 species).We examined their effect of some biological activities of MP.Results were as follows.(1) All the synthesized peptides in this study had no catecholamine (CA) releasing activity, activity of GTP ase activation or hemolytic activity.(2) N-4 and C-4 fragments both inhibited MP-and acetylcholine (ACh)-stimulated CA-release from chromaffin cells with a bath application system. From the inhibitory effect on some kinds of agonists-stimulated CA-release, it is concluded that N-4 and C-4 fragments selectively inhibit the nicotinic secretory response by attacking the nicotinic ACh receptors (nAChR) on the site (s) other than ACh binding site.(3) From the structure and function-releationship of N-4 analogs, the site (s) on nAChR attacked by N-4 are suggested to be made of hydrophobic amino acids and acidic amino acids. One of the analogs was about five times as strong as N-4 in nAChR inhibitory activity.(4) MP-stimulated GTP ase activity was inhibited by C-4 but not by N-4.therefore, CA release evoked by MP from chromaffin cells is supposed to be mediated by an unknown exocytotic process.As the next process of this work, we will approach to a possibly of these newly synthesized peptides to act effectively on several certain disease.