Characterization of the endokinins: Human tachykinins with cardiovascular activity

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  • Nigel M. Page
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom
  • Nicola J. Bell
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom
  • Sheila M. Gardiner
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom
  • Isaac T. Manyonda
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom
  • Kerensa J. Brayley
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom
  • Philip G. Strange
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom
  • Philip J. Lowry
    School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; and Department of Obstetrics and Gynecology, St. George's Hospital, London SW17 0QT, United Kingdom

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<jats:p> We report four human tachykinins, endokinins A, B, C, and D (EKA–D), encoded from a single tachykinin precursor 4 gene that generates four mRNAs (α, β, γ, and δ). Tachykinin 4 gene expression was detected primarily in adrenal gland and in the placenta, where, like neurokinin B, significant amounts of EKB-like immunoreactivity were detected. EKA/B 10-mers displayed equivalent affinity for the three tachykinin receptors as substance P (SP), whereas a 32-mer N-terminal extended form of EKB was significantly more potent than EKA/B or SP. EKC/D, which possess a previously uncharacterized tachykinin motif, FQGLL-NH <jats:sub>2</jats:sub> , displayed low potency. EKA/B displayed identical hemodynamic effects to SP in rats, causing short-lived falls in mean arterial blood pressure associated with tachycardia, mesenteric vasoconstriction, and marked hindquarter vasodilatation. Thus, EKA/B could be <jats:italic>the</jats:italic> endocrine/paracrine agonists at peripheral SP receptors and there may be as yet an unidentified receptor(s) for EKC/D. </jats:p>

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