PT  - JOURNAL ARTICLE
AU  - D P Geraghty
AU  - C J Mussap
AU  - E Burcher
TI  - Radioiodinated substance P, neurokinin A, and eledoisin bind predominantly in NK1 receptors in guinea pig lung.
DP  - 1992 Jan 01
TA  - Molecular Pharmacology
PG  - 147--153
VI  - 41
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/41/1/147.short
4100  - http://molpharm.aspetjournals.org/content/41/1/147.full
SO  - Mol Pharmacol1992 Jan 01; 41
AB  - In homogenates of guinea pig lung, binding of 125I-Bolton-Hunter-labeled substance P (BHSP), Bolton-Hunter-labeled eledoisin (BHELE), and [125I]iodohistidyl neurokinin A (INKA) was investigated. Equilibrium dissociation constants (derived from "cold" saturation experiments) for BHSP, INKA, and BHELE were 0.96 +/- 0.15, 1.61 +/- 0.26, and 1.98 +/- 0.12 nM, respectively. Specific binding of all three radioligands was increased 2-3-fold by 10 microM phosphoramidon. The rank order of potency of unlabeled tachykinins in competing against BHSP was substance P (SP) greater than [Sar9,Met(O2)11]-SP greater than SP methyl ester greater than neuropeptide gamma greater than neurokinin A greater than or equal to neurokinin B = kassinin greater than or equal to eledoisin greater than or equal to scyliorhinin II much greater than neuropeptide K, indicating binding to sites with the general characteristics of NK1 receptors. Similar rank potency orders were observed for INKA and BHELE, showing binding to NK1 sites, rather than to NK2 or NK3 sites, which are labeled with high affinity by these radioligands in other tissues. For all radioligands, competition curves for SP and the NK1-selective agonist [Sar9,Met(O2)11]-SP could be resolved into two components, representing high and low affinity binding sites. These were present in the approximate ratios 2:3 (for BHSP), 1:1 (for INKA), and 8:1 (for BHELE). Other agonist competition curves also yielded high and low affinity components. The data suggest that BHSP and INKA bind partly and BHELE predominantly to high affinity NK1 receptors. The nature of the low affinity site(s) could be another tachykinin receptor or a low affinity state of the NK1 receptor. Binding to a "classical" NK2 receptor is unlikely, because selective NK2 receptor antagonists and analogs were very weak competitors. Our data suggest that, in addition to the NK1 receptor, another type of tachykinin receptor may exist in this tissue. The inability to detect NK2 binding sites is strikingly at variance with functional studies.