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Effect of the tachykinin antagonist, [abetd-Pro4, abetd-Trp7,9,10] substance P-(4–11), on tachykinin- and histamine-induced inositol phosphate generation in intestinal smooth muscle

Naunyn-Schmiedeberg's Archives of Pharmacology volume 335, pages 296–300 (1987)Cite this article

Summary

  1. 1.

    The effect of the tachykinin antagonist, [abetd-Pro4, abetd-Trp7,9,10]substance P-(4–11), on inositol phosphate accumulation produced by tachykinins and by histamine in strips of longitudinal muscle from the guinea-pig small intestine was investigated in the presence of 12 mM Li+.

  2. 2.

    The two tachykinins substance P (SP) and kassinin (20 nM – 20 μM) caused an accumulation of inositol phosphates in a concentration-dependent manner. This was seen with an agonist contact time of only 30 s. SP and kassinin were roughly equipotent in inducing inositol phosphate accumulation, which is consistent with their relative potencies in causing muscle contraction.

  3. 3.

    The tachykinin antagonist (20 μM) produced a shift to the right of the dose-response curves for inositol phosphate accumulation caused by SP and kassinin. However, the effect of kassinin was inhibited much more than that of SP, which is consistent with a similar differential antagonism of the contractions induced by these agonists.

  4. 4.

    The tachykinin antagonist also depressed histamine-induced accumulation of inositol phosphates whereas histamine-induced contractions had previously been found unaffected by the antagonist.

  5. 5.

    These findings show that the tachykinin antagonist is not totally selective with regard to agonist-induced accumulation of inositol phosphates in intestinal smooth muscle. This may suggest that the antagonist not only acts on tachykinin receptors but also has another site of cellular action.

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Author notes

  1. S. J. Bailey

    Present address: University Department of Experimental and Clinical Pharmacology, Universitätsplatz 4, A-8010, Graz, Austria

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  1. University Department of Experimental and Clinical Pharmacology, K. Thomae GmbH, Abteilung Biochemie, Postfach 1755, D-79500, Biberach an der RiB, Federal Republic of Germany

    S. J. Bailey, Irmgard Th. Lippe & P. Holzer

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  1. S. J. Bailey
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Bailey, S.J., Lippe, I.T. & Holzer, P. Effect of the tachykinin antagonist, [abetd-Pro4, abetd-Trp7,9,10] substance P-(4–11), on tachykinin- and histamine-induced inositol phosphate generation in intestinal smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 335, 296–300 (1987). https://doi.org/10.1007/BF00172800

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  • DOI: https://doi.org/10.1007/BF00172800

Key words

  • Substance P
  • Kassinin
  • Histamine
  • Tachykinin agonists
  • Tachykinin antagonists
  • Tachykinin receptors
  • Phosphoinositide metabolism
  • Accumulation of inositol phosphates
  • Contraction mechanism
  • Intestinal smooth muscle