Characterisation of a novel, selective radioligand, [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]neurokinin A-(4-10), for the tachykinin NK2 receptor in rat fundus

Eur J Pharmacol. 1993 Mar 23;233(2-3):201-7. doi: 10.1016/0014-2999(93)90051-i.

Abstract

The tyrosyl derivative of the tachykinin NK2 selective agonist [Lys5,MeLeu9,Nle10]NKA-(4-10) was iodinated and the product [125I][Lys5,Tyr(I2)2,MeLeu9,Nle10]NKA-(4-10) purified using reverse phase HPLC. The binding characteristics of this novel radioligand were investigated in homogenates of rat gastric fundus. Binding was saturable, reversible and to a single population of high affinity sites of KD 1.3 +/- 0.2 nM (n = 4). Specific binding of [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4-10) was inhibited by neuropeptide gamma SR 48968 > or = neurokinin A (NKA) > or = [Lys5,MeLeu9,Nle10]NKA-(4-10) > [Lys5,Tyr7,MeLeu9,Nle10] NKA-(4-10) > neuropeptide K > [Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4-10) > MDL 29,913 > [127I]- Bolton-Hunter-NKA > neurokinin B > substance P (SP) >> MEN 10207 > [Sar9,Met(O2)11]SP >> senktide, indicating binding to NK2 receptors. NKA, [Lys5,MeLeu9,Nle10]NKA-(4-10) and [Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4-10) contracted the isolated fundus strip, with pD2 values 7.9, 7.7 and 7.4, respectively. This novel, highly selective radioligand should prove useful in characterisation studies in peripheral tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / drug effects*
  • Brain / metabolism
  • Chromatography, High Pressure Liquid
  • Female
  • Gastric Fundus / drug effects
  • Gastric Fundus / metabolism
  • Male
  • Neurokinin A / analogs & derivatives*
  • Neurokinin A / chemical synthesis
  • Neurokinin A / metabolism
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / metabolism*
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-2
  • Receptors, Neurotransmitter / drug effects*
  • Receptors, Neurotransmitter / metabolism

Substances

  • Peptide Fragments
  • Receptors, Neurokinin-2
  • Receptors, Neurotransmitter
  • neurokinin A (4-10), Lys(5)-Tyr(I2)(7)-MeLeu(9)-Nle(10)-
  • Neurokinin A