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Species differences in tachykinin receptor distribution: Further evidence that the substance P (NK1) receptor predominates in human brain

Authors

  • Michael Rigby,

    Corresponding author
    1. In Vivo Neuroscience, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, United Kingdom
    • In Vivo Neuroscience, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK
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  • Ruth O'Donnell,

    1. Molecular and Cellular Neuroscience, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, United Kingdom
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  • Nadia M.J. Rupniak

    1. Dynogen Pharmaceuticals, Inc., Research Triangle Park, Durham, North Carolina 27709
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Abstract

Marked species differences in the distribution of central tachykinin receptors are reported but uncertainty remains about the ability of available ligands to detect NK2 and NK3 receptors in human brain. We compared the distribution of NK1, NK2, and NK3 receptors in sections from rodent, primate, and human brain using the 125I-labeled ligands substance P (SP) for the NK1 receptor, neurokinin A (NKA) for the NK2 receptor, and neurokinin B (NKB) and eledoisin for NK3 receptors. Duration of exposure to autoradiographic film was from 7 days for [125I]SP up to 90 days for the other ligands. High levels of specific [125I]SP binding were seen throughout the brains of all species studied. Specific [125I]NKA binding was detected in brains from neonatal rat, and to a lesser level in adult rat, gerbil, and guinea pig; it was not detected in monkey or human brain, but was present in circular muscle of human duodenum, confirming that this ligand binds to human NK2 receptors under our experimental conditions. Specific [125I]NKB and [125I]eledoisin binding was widespread in brain sections from rats, gerbils, and guinea pigs, and very low levels were also detected in marmoset, squirrel monkey, and rhesus monkey brain after prolonged (up to 90 days) exposure. We failed to identify specific eledoisin binding in human brain, even after prolonged exposures. These findings demonstrate that the NK1 receptor is the predominant tachykinin receptor expressed in primate and human brain, but that low levels of NK3 receptor are present in nonhuman, primate brain. J. Comp. Neurol. 490:335–353, 2005. © 2005 Wiley-Liss, Inc.

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