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Radioiodinated substance P, neurokinin A, and eledoisin bind predominantly in NK1 receptors in guinea pig lung


Geraghty, DP and Mussap, CJ and Rogerson, FM and Burcher, E, Radioiodinated substance P, neurokinin A, and eledoisin bind predominantly in NK1 receptors in guinea pig lung, Molecular Pharmacology, 41, (1) pp. 147-153. ISSN 0026-895X (1992) [Refereed Article]


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

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Geraghty, DP (Professor Dominic Geraghty)
ID Code:69037
Year Published:1992
Web of Science® Times Cited:44
Deposited By:Health Sciences A
Deposited On:2011-04-15
Last Modified:2011-11-21

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