NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi

Amadesi, S., Moreau, J., Tognetto, M., Springer, J., Trevisani, M., Naline, E., Advenier, C., Fisher, A., Vinci, D., Mapp, C., Miotto, D., Cavallesco, G. and Geppetti, P. (2001) NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi. American Journal of Respiratory and Critical Care Medicine, 163 (5). pp. 1206-1211. ISSN 1535-4970 doi: 10.1164/ajrccm.163.5.2002079

Abstract/Summary

Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human isolated bronchi. Specific staining was seen in bronchial sections with an antibody directed against the human NK1 receptor. The selective NK1 receptor agonist, [Sar(9), Met(O2)(11)]SP, contracted about 60% of human isolated bronchial rings. This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar(9), Met(O2)(11)]SP was independent of acetylcholine and histamine release and epithelium removal, and was not affected by nitric oxide synthase and cyclooxygenase (COX) inhibition. [Sar(9), Met(O2)(11)]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size (approximately 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar(9), Met(O2)(11)]SP in small-size, but not in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large proportion of medium-size human bronchi. Unlike small-size bronchi this effect is independent of prostanoid release, and the results are suggestive of a direct activation of smooth muscle receptors and IP release.

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Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/35822
Item Type	Article
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
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Publisher	American Thoracic Society
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