[3H][beta-Ala8]neurokinin A-(4-10): a novel, selective radioligand for the tachykinin NK2 receptor

Eur J Pharmacol. 1995 Dec 27;294(1):239-45. doi: 10.1016/0014-2999(95)00529-3.

Abstract

The binding characteristics of the novel radioligand [3H][beta-Ala8]neurokinin A-(4-10) were assessed in hamster urinary bladder membranes. This labelled compound bound in a reversible, highly specific and concentration-dependent manner to a single class of high affinity binding sites with a Kd of 1.8 +/- 0.2 nM and a Bmax of 139 +/- 21 fmol/mg of protein. Specific binding of [3H][beta-Ala8]neurokinin A-(4-10) was displaced only by NK2, but not by NK1 or NK3, tachykinin receptor agonists and antagonists. Neurokinin A, [beta-Ala8]neurokinin A-(4-10), L 659877 [cyclo(Leu-Met-Gln-Trp-Phe-Gly)], MEN 10376 (H-Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH2), MEN 10627 [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta)] and SR 48968 [(S)-N-methyl-N-[4-(4-acetylamino-4-phenylpiperidino)-2- (3,4-dichlorophenyl)butyl]benzamide] displaced the binding with Ki values of 0.4 +/- 0.1 nM, 1.9 +/- 0.36 nM, 3.05 +/- 0.1 nM, 7.9 +/- 0.4 microM, 0.36 +/- 0.02 nM and 2.5 +/- 0.9 nM, respectively. Functional data, obtained in isolated hamster urinary bladder strips with the newly developed tachykinin NK2 receptor antagonists (MEN 10627 and SR 48968), showed a good agreement with binding data. This novel radioligand could represent a new useful tool for the assessment of tachykinin NK2 receptor antagonists.

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Binding, Competitive / drug effects
  • Cricetinae
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Mesocricetus
  • Muscle Contraction / drug effects
  • Neurokinin A / analogs & derivatives*
  • Neurokinin A / pharmacology
  • Peptide Fragments / pharmacology*
  • Peptides, Cyclic / pharmacology
  • Piperidines / pharmacology
  • Receptors, Neurokinin-1 / metabolism
  • Receptors, Neurokinin-2 / antagonists & inhibitors*
  • Receptors, Neurokinin-3 / metabolism
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism

Substances

  • Benzamides
  • Ligands
  • Peptide Fragments
  • Peptides, Cyclic
  • Piperidines
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • neurokinin A (4-10), beta-Ala(8)-
  • MEN 10627
  • SR 48968
  • Neurokinin A