The roles of the N-terminal portions of various tachykinins in promoting salivation.
OBJECTIVE
In order to determine the active sites for salivation of various tachykinins, the regulatory roles of the N-terminal portion of various newly-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. Amino acids were eliminated one by one to form octa- to undeca-peptides adjoining the inactive or less active heptapeptides and various heptapeptides, in which an amino acid in position 8 (Xaa8), numbering as in an undecapeptide, was replaced with Tyr, Phe, Ile or Val.


RESULTS
The N-terminal amino acids in positions 1 to 4 could be activators or inhibitors, depending on whether the C-terminal heptapeptide was inactive or less active. The Xaa8 residue, in combination with amino acids in positions 5 and 6, seemed to be very important in determining the sialogogic activity of a heptapeptide. The discrimination between NKA and NKB appeared due to the N-terminal amino acid sequence in positions I to 4 including Phe or Ser in position 6.


CONCLUSIONS
It is concluded that the N-terminal amino acids in positions I to 4 serve as either activators or inhibitors depending upon the sialogogic activity of the C-terminal heptapeptide, in which particular amino acids in positions 5, 6 and 8 regulate its activity.
Higa
K
K
Department of Pediatric Dentistry, Fukuoka Dental College, Japan.
Gao
C
C
Motokawa
W
W
Abe
K
K
D000704:Analysis of Variance; D000818:Animals; D004600:Eledoisin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007532:Isoleucine / Q000494:pharmacology; D015286:Kassinin / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects*; D012694:Serine / Q000494:pharmacology; D013223:Statistics as Topic; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism; D015320:Tachykinins / Q000008:administration & dosage / Q000494:pharmacology*; D014443:Tyrosine / Q000494:pharmacology; D014633:Valine / Q000494:pharmacology
D015320:Tachykinins; D007532:Isoleucine; D014443:Tyrosine; D012694:Serine; D010649:Phenylalanine; D015286:Kassinin; D004600:Eledoisin; D015288:Neurokinin A; D015287:Neurokinin B; D014633:Valine