Characterization of the binding sites of [3H]SR 48968, a potent nonpeptide radioligand antagonist of the neurokinin-2 receptor

Biochem Biophys Res Commun. 1993 Mar 31;191(3):1172-7. doi: 10.1006/bbrc.1993.1340.

Abstract

[3H]SR 48968, a radiolabeled nonpeptide antagonist of NK-2 receptor, has been tested in ligand-receptor binding assays using rat duodenum, hamster urinary bladder and guinea pig ileum membranes. [3H]SR 48968 bound to a single class of high affinity binding sites. Its affinity was slightly species-dependent. Its binding was inhibited by neurokinins, following the rank order of potency NKA > NKB > SP. It was also inhibited by peptide antagonists of NK-2 receptor (MEN 10,376, L 659,877), but their relative potencies were highly species-dependent. Unlabeled SR 48968, but not its R-enantiomer (SR 48965), also potently inhibited its binding. These data show that [3H]SR 48968 potently binds to NK-2 receptor and therefore is a useful tool to study NK-2 receptor.

MeSH terms

  • Animals
  • Benzamides / metabolism*
  • Binding Sites
  • Binding, Competitive
  • Cricetinae
  • Duodenum / metabolism
  • Guinea Pigs
  • In Vitro Techniques
  • Kinetics
  • Mesocricetus
  • Piperidines / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neurokinin-2
  • Receptors, Neurotransmitter / antagonists & inhibitors*
  • Receptors, Neurotransmitter / metabolism
  • Substance P / antagonists & inhibitors*
  • Urinary Bladder / metabolism

Substances

  • Benzamides
  • Piperidines
  • Receptors, Neurokinin-2
  • Receptors, Neurotransmitter
  • Substance P
  • SR 48968