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

Amadesi, Silvia, Moreau, Joelle, Tognetto, Michele, Springer, Jochem, Trevisani, Marcello, Naline, Emmanuel, Advenier, Charles, Fisher, Axel, Vinci, Damiano, Mapp, Cristina, Miotto, Deborah, Cavallesco, Giorgio and Geppetti, Pierangelo (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 1073-449X

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Abstract

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.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	Rhiannon Harvey
Date Deposited:	09 Jun 2011 14:57
Last Modified:	24 Oct 2022 03:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/32121
DOI:	10.1164/ajrccm.163.5.2002079

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