The effect of thiorphan and epithelium removal on contractions and tachykinin release produced by activation of capsaicin-sensitive afferents in the guinea-pig isolated bronchus |
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Authors: | Maggi Carlo Alberto Patacchini Riccardo Perretti Francesca Meini Stefania Manzini Stefano Santicioli Paolo Del Bianco Elena Meli Alberto |
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Affiliation: | (1) Pharmacology Department, Smooth Muscle Division, Research Laboratories, A. Menarini Pharmaceuticals, Via Sette Santi 3, I-50131 Florence;(2) Malesci Pharmaceuticals, Florence;(3) Department of Internal Medicine, University of Florence, Italy |
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Abstract: | Summary (1) We have studied the effect of epithelium removal (rubbing) and the endopeptidase 24.11 inhibitor, thiorphan, on the contractile response of the guinea-pig isolated bronchi (atropine and indomethacin in the bath) produced by electrical field stimulation, capsaicin or exogenously administered tachykinins (substance P and neurokinin A). (2) The response to field stimulation, thought to involve release of endogenous tachykinins, was potentiated by thiorphan in both epithelium-free and intact bronchi. However, at low frequencies (1–5 Hz), the effect of thiorphan was more evident in intact preparations. (3) The response to capsaicin was enhanced by both epithelium removal and thiorphan administration. (4) The response to exogenous substance P or neurokinin A was potentiated by thiorphan both in epithelium-free and intact bronchi. (5) Capsaicin (1 M) evoked a consistent release of substance P-like immumoreactivity (determined by radioimmunoassay) and tachykinin-like immumoreactivity (determined by a novel immumoenzyme assay), which was enhanced by thiorphan in both epithelium-free and intact bronchi. (6) These findings suggest that a thiorphan-sensitive mechanism, presumably enkephalinase (endopeptidase 24.11), plays a major role in inactivating endogenous tachykinins released from sensory nerves and that this enzymatic activity is still present after removal of the bronchial epithelium.Send offprint requests to C. A. Maggi at the above address |
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Keywords: | Capsaicin /content/v01t726854w47722/xxlarge8216.gif" alt=" lsquo" align=" BASELINE" BORDER=" 0" >Efferent /content/v01t726854w47722/xxlarge8217.gif" alt=" rsquo" align=" BASELINE" BORDER=" 0" > function of sensor nerves Thiorphan Guinea-pig bronchi Tachykinins Endopeptidase 24.11 |
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