Parallel bioassay of 39 tachykinins on 11 smooth muscle preparations. Structure and receptor selectivity/affinity relationship

Peptides. 2000 Nov;21(11):1587-95. doi: 10.1016/s0196-9781(00)00290-4.

Abstract

Parallel bioassay on smooth muscle preparations demonstrated that: all TKs having a neutral or basic residue at position 7 from the C-terminus show a clear-cut preference for the NK1 TK receptor, reinforced by the presence of the aromatic doublet Phe-Phe or Phe-Tyr (aromatic TKs); all aliphatic TKs (Phe-Ile/Val) having an acidic residue at position 7 show a clear-cut preference for NK2/NK3 receptors, generally without selectivity for a single receptor. However, in aromatic TKs having the same acidic residue, the preference for NK2/NK3 receptors is weakened, with a more or less pronounced co-preference for the NK1 receptor. Amino acid substitutions in the C-terminal tripeptide may influence receptor affinity.

MeSH terms

  • Animals
  • Biological Assay
  • Guinea Pigs
  • Isoleucine
  • Male
  • Mice
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Phenylalanine / chemistry
  • Proline / chemistry
  • Protein Binding
  • Rabbits
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-1 / metabolism
  • Receptors, Neurokinin-2 / metabolism
  • Receptors, Neurokinin-3 / metabolism
  • Receptors, Tachykinin / metabolism
  • Tachykinins / chemistry*
  • Tachykinins / metabolism*
  • Tachykinins / pharmacology
  • Tyrosine / chemistry

Substances

  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • Receptors, Tachykinin
  • Tachykinins
  • Isoleucine
  • Tyrosine
  • Phenylalanine
  • Proline