Effect of scyliorhinin I and synthetic scyliorhinin I derivatives at mammalian tachykinin NK1, NK2 and NK3 receptors

Eur J Pharmacol. 1993 Dec 7;250(2):311-6. doi: 10.1016/0014-2999(93)90396-y.

Abstract

The dogfish tachykinin peptide scyliorhinin I and a number of its analogues substituted in position 7 were tested in bioassays for tachykinin NK1, NK2 and NK3 receptors. Scyliorhinin I behaved as a full agonist at tachykinin NK1 receptors of the guinea-pig ileum longitudinal muscle and at NK2 receptors of the rabbit pulmonary artery and hamster trachea. In these three preparations scyliorhinin I was as potent agonist as substance P methylester and neurokinin A, respectively. Evidence for activation of tachykinin NK1 and NK2 receptors by scyliorhinin I was obtained by using the selective tachykinin antagonists FK 888, MEN 10,376 and L 659,877. Scyliorhinin I was poorly active as an agonist at NK3 receptors of the rat portal vein. Among scyliorhinin I analogues, [beta-(2-naphthyl)-Ala7]scyliorhinin I, [Val7]scyliorhinin I and [Ile7]scyliorhinin I were 3-25 times weaker than scyliorhinin I itself at NK1 and NK2 receptors. [Phe7]scyliorhinin I, [Phe(F)7]scyliorhinin I and [Phe(Cl)7]scyliorhinin I were as potent as scyliorhinin I at NK1 receptors in the guinea-pig ileum, while they showed 10-30 times lower affinity than scyliorhinin I for NK2 receptors. The present results are discussed in relation to the importance of position 7 in determining the potency and selectivity of scyliorhinin I analogues at tachykinin receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cricetinae
  • Dipeptides / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Indoles / pharmacology
  • Male
  • Mesocricetus
  • Molecular Sequence Data
  • Neurokinin A / analogs & derivatives
  • Neurokinin A / pharmacology
  • Neurokinin-1 Receptor Antagonists
  • Peptide Fragments / pharmacology
  • Peptides, Cyclic / pharmacology
  • Rabbits
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-1 / drug effects*
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Receptors, Neurokinin-2 / drug effects*
  • Receptors, Neurokinin-3 / antagonists & inhibitors
  • Receptors, Neurokinin-3 / drug effects*
  • Substance P / antagonists & inhibitors
  • Tachykinins / antagonists & inhibitors
  • Tachykinins / pharmacology*

Substances

  • Dipeptides
  • Indoles
  • Neurokinin-1 Receptor Antagonists
  • Peptide Fragments
  • Peptides, Cyclic
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • Tachykinins
  • scyliorhinin I
  • cyclo(Gln-Trp-Phe-Gly-Leu-Met)
  • neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-
  • FK 888
  • Substance P
  • Neurokinin A