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A novel substance P binding site in bovine adrenal medulla


Geraghty, DP and Livett, BG and Rogerson, FM and Burcher, E, A novel substance P binding site in bovine adrenal medulla, Neuroscience Letters, 112, (2-3) pp. 276-281. ISSN 1872-7972 (1990) [Refereed Article]

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DOI: doi:10.1016/0304-3940(90)90216-V


Radioligand binding techniques were used to characterize the substance P (SP) binding site on membranes prepared from bovine adrenal medullae. 125I-labelled Bolton-Hunter substance P (BHSP), which recognises the C-terminally directed, SP-preferring NK1 receptor, showed no specific binding. In contrast, binding of [3H]SP was saturable (at 6 nM) and reversible, with an equilibrium dissociation constant (Kd) 1.46 +/- 0.73 nM, Bmax 0.73 +/- 0.06 pmol/g wet weight and Hill coefficient 0.98 +/- 0.01. Specific binding of [3H]SP was displaced by SP greater than neurokinin A (NKA) greater than SP(3-11) approximately SP(1-9) greater than SP(1-7) approximately SP(1-4) approximately SP(1-6), with neurokinin B (NKB) and SP(1-3) very weak competitors and SP(5-11), SP(7-11) and SP(9-11) causing negligible inhibition (up to 10 microM). This potency order is quite distinct from that seen with binding to an NK1 site, a conclusion confirmed by the lack of BHSP binding. It appears that Lys3 and/or Pro4 are critical for binding, suggesting an anionic binding site. These data suggest the existence of an unusual binding site which may represent a novel SP receptor. This site appears to require the entire sequence of the SP molecule for full recognition.

Item Details

Item Type:Refereed Article
Keywords:Substance P; Radioligand binding; Bovine adrenal medulla; Tachykinin receptor
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:69030
Year Published:1990
Web of Science® Times Cited:32
Deposited By:Health Sciences A
Deposited On:2011-04-15
Last Modified:2011-04-19

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