Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Legat, FJ; Griesbacher, T; Lembeck, F.
CP-96,345, a non-peptide antagonist of substance P: I. Effects on the actions mediated by substance P and related tachykinins on the guinea-pig ileum and rabbit jejunum.
Naunyn Schmiedebergs Arch Pharmacol. 1992; 346(3):315-322
Doi: 10.1007/BF00173545
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- Führende Autor*innen der Med Uni Graz
- Legat Franz
- Lembeck Fred
- Co-Autor*innen der Med Uni Graz
- Griesbacher Thomas
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- Abstract:
- The effects of a non-peptide antagonist of substance P, CP-96,345, were investigated, in vitro, on the guinea-pig ileum and the rabbit jejunum. Contractions of the guinea-pig ileum, induced by substance P and neurokinin A, were specifically inhibited by the racemate (+/-)CP-96,345 (pIC50 7.8 and 7.3, respectively). The inhibition by (+/-)CP-96,345 of contractions evoked by neurokinin B and by bradykinin (pIC50 6.1 and 4.9, respectively) was attributed to unspecific effects of the antagonist. The inhibition of substance P-induced contractions of the rabbit jejunum required a 10 times higher concentration of (+/-)CP-96,345 (pIC50 = 6.8) than was required with the guinea-pig ileum. The plateau phase of contraction of the guinea-pig ileum induced by high concentrations of substance P, neurokinin A or neurokinin B, which is known to be mediated through tachykinin receptors on intrinsic cholinergic neurones, was inhibited by 200 nM (+/-)CP-96,345 but not by the inactive enantiomer, CP-96,344. This indicates a specific inhibition of these neuronal tachykinin receptors by (+/-)CP-96,345. Contractions known to be mediated by the release of substance P, such as those evoked by capsaicin and by mesenteric nerve or field stimulation, were partially inhibited by (+/-)CP-96,345 at concentrations of 200 to 600 nM. Unspecific inhibitory effects of CP-96,345, in concentrations of 1 microM or higher, were observed on histamine-induced contractions, and on the cholinergic twitch response to electrical stimulation, of the guinea-pig ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Biphenyl Compounds - pharmacology
- Capsaicin - pharmacology
- Electric Stimulation -
- Guinea Pigs -
- Hexamethonium Compounds - pharmacology
- Histamine - pharmacology
- Ileum - drug effects
- In Vitro Techniques -
- Jejunum - drug effects
- Muscle Contraction - drug effects
- Muscle, Smooth - drug effects
- Parasympathetic Nervous System - drug effects
- Peristalsis - drug effects
- Rabbits -
- Stereoisomerism -
- Substance P - antagonists & inhibitors
- Substance P - physiology
- Tachykinins - pharmacology
- Tachykinins - physiology