The roles of the N-terminal portions of various tachykinins in promoting salivation

OBJECTIVES: In order to determine the active sites for salivation of variou s tachykinins, the regulatory roles of the N-terminal portion of various ne wly-synthesized tachykinins were studied after i.p. injection of rats using the submandibular glands as model organs. METHODS: N-shortened oligopeptides from kassinin, eledoisin, neurokinins A (NKA) and NKB were synthesized by the multipin peptide synthesis method. Am ino acids were eliminated one by one to form octa- to undeca-peptides adjoi ning the inactive or less active heptapeptides and various heptapeptides, i n which an amino acid in position 8 (Xaa(8)), numbering as in an undecapept ide, was replaced with Tyr, Phe, lie or Val. RESULTS: The N-terminal amino acids in positions I to 4 could be activators or inhibitors, depending on whether the C-terminal heptapeptide was inacti ve or less active. The Xaa(8) residue, in combination with amino acids in p ositions 5 and 6, seemed to be very important in determining the sialogogic activity of a heptapeptide. The discrimination between NKA and NKB appeare d due to the N-terminal amino acid sequence in positions 1 to 4 including P he or Ser in position 6. CONCLUSIONS: It is concluded that the N-terminal amino acids in positions 1 to 4 serve as either activators or inhibitors depending upon the sialogogi c activity of the C-terminal heptapeptide, in which particular amino acids in positions 5, 6 and 8 regulate its activity.