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Synthesis and Biological Activity of Agonists for the Neuronal Tachykinin Receptor in Guinea Pig Ileum

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Substance P and Neurokinins

Abstract

The classification of tachykinin receptors into two subclasses, the SP-P and the SP-E receptors has been well established (1). Recently Laufer et. al. (2) characterized, in the guinea pig ileum, a third tachykinin receptor subclass, designated as SP-N receptor. The SP-N receptor is located on the enteric cholinergic neurons, and madiates the release of acetylcholine. We found that the SP analog (pGlu6,(N-Me)Phe8) SP6-11 acts as a selective potent agonist for the SP-N receptor (EC50=0.5 nM) while its potency for the SP-P receptor is much lower (EC50=500 nM). Conceivably N-methylation of Phe8 in the hexapeptide sequence of substance P (SP), induces selectivity toward the SP-N receptor. Therefore we set to probe the constraints at the nitrogen of Phe7-Phe8 amide bond by changing the alkyl group at this site.

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References

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Author information

Authors and Affiliations

  1. Dept. of Pharmaceutical, The Hebrew University, 91120, Jerusalem, Israel

    D. Ron & M. Chorev

  2. Dept. of Biological, The Hebrew University, 91120, Jerusalem, Israel

    R. Laufer, J. Frey & Z. Selinger

  3. Dept. of Organic Chemistry, The Hebrew University, 91120, Jerusalem, Israel

    C. Gilon

Authors
  1. D. Ron
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  2. R. Laufer
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  3. J. Frey
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  4. C. Gilon
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  5. Z. Selinger
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  6. M. Chorev
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Editor information

Editors and Affiliations

  1. Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    James L. Henry Ph.D.

  2. Department of Physiology, University of Montreal, C.P. 6208, Montreal, Quebec, H3C 3T8, Canada

    Rejean Couture Ph.D.

  3. Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    A. Claudio Cuello M.D.

  4. MRC Group in Molecular Endocrinology, Centre Hospitalier de L’Universite, Laval, Quebec, G1V 4G2, Canada

    Georges Pelletier Ph.D.

  5. Douglas Hospital Research Centre and Department of Psychiatry, McGill University, Verdun, Quebec, H4H 1R3, Canada

    Remi Quirion Ph.D.

  6. Department of Pharmacology, Medical School, University of Sherbrooke, Sherbrooke, Quebec, J1H 5N4, Canada

    Domenico Regoli M.D.

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© 1987 Springer-Verlag New York Inc.

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Ron, D., Laufer, R., Frey, J., Gilon, C., Selinger, Z., Chorev, M. (1987). Synthesis and Biological Activity of Agonists for the Neuronal Tachykinin Receptor in Guinea Pig Ileum. In: Henry, J.L., Couture, R., Cuello, A.C., Pelletier, G., Quirion, R., Regoli, D. (eds) Substance P and Neurokinins. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-4672-5_48

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  • DOI: https://doi.org/10.1007/978-1-4612-4672-5_48

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-9109-1

  • Online ISBN: 978-1-4612-4672-5

  • eBook Packages: Springer Book Archive

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