Sialogogic activity in the rat of peptides analogous to [Tyr(8)]-substanceP in which substitutions have been made in the N-terminal amino acids

In order to elucidate the regulatory roles for salivation of amino acids in positions 1-4 of the N-terminal region of [Tyr(8)]-substance P (SP), the s tructure-sialogogic activity correlations of various synthetic octa- to und ecapeptides replaced in positions 1-4 of [Tyr(8)]-SP with each of 19 common amino acids, one by one, and with the same sequence of the C-terminal hept apeptide as that of [Tyr(8)]-SP, were studied in the submandibular glands o f rats after intraperitoneal injection. Each of 19 octa-, nona-, deca- and undecapeptides with replaced amino acids and a pentato decapeptide with the progressive elimination of the N-terminal portion were newly synthesized b y the multipin peptide method, All octa- to undecapeptides replaced with ea ch of 19 common amino acids in positions 1-4 had sialogogic activities, In 19 octa- and decapeptides in which P-4 and P-2 had been replaced, four and three replacements, respectively, had significantly increased secretory act ivities. In contrast, in 19 nonapeptides in which K-3 had been replaced, no ne had significantly increased secretory activities.. Furthermore, in 19 un decapeptides in which R-1 had been replaced, most replacements had signific antly increased or equipotent activities for fluid secretion. It is conclud ed that amino acids in the N-terminal legion of various tachykinins may not need to be strictly conserved and that amino acid residues in the N-termin al portion, R-1 in particular and P-2, may strongly inhibit secretory activ ity. (C) 2001 Elsevier Science Ltd. All lights reserved.