Heterogeneity of tachykinin receptors in the rabbit lung

Susan L. Millard, John W. Bloom, Henry I. Yamamura

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Abstract

The tachykinins, substance P (SP) and neurokinin A (NKA), are agonists for the NK1 and NK2 receptors, respectively. Tachykinins have various respiratory effects, including bronchoconstriction. This study characterizes tachykinin binding sites in the rabbit lung. We hypothesize that (2[125I]iodohistidyl1)Neurokinin A ([125I]NKA) interacts with NK1 and NK2 binding sites in the rabbit lung. The K(d) determined from saturation isotherms was 0.69 x// 1.14 nM (geometric mean x// SEM) and the B(max) was 4.15 ± 0.22 femtomole/mg protein (arithmetic mean ± SEM). Competitive inhibition studies with NKA, SP and various selective tachykinin agonists showed the rank order of potency: [β-Ala8]-Neurokinin A 4-10 = SP >> NKA >> [Sar9,Met(O2)11]-Substance P. [β-Ala8]-Neurokinin A 4-10, a selective NK2 agonist, and SP inhibition of [125I]NKA binding were best described using a two-site model. Competitive inhibition studies using the selective nonpeptide NK2 antagonist (SR 48968) and the selective nonpeptide NK1 antagonist (CP 96,345) revealed K(i)'s of 5.5 nM and 8.1 nM, respectively. Our data therefore suggest that [125I]NKA binds to both the NK1 and NK2 receptors in the lung.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalNeurochemical Research
Volume21
Issue number2
DOIs
StatePublished - Feb 1 1996

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Keywords

  • Tachykinins
  • neurokinin A
  • rabbit lung
  • radioligand binding
  • substance P

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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