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

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

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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.
Original languageEnglish
Pages (from-to)1206-1211
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume163
Issue number5
DOIs
Publication statusPublished - Apr 2001

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