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Am. J. Respir. Crit. Care Med., Volume 163, Number 5, April 2001, 1206-1211

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, and PIERANGELO GEPPETTI

Pharmacology Unit, Department of Experimental and Clinical Medicine, University of Ferrara, Italy; Department of Surgery, Az. Ospedaliera S. Anna, Ferrara, Italy; Department of Pharmacology, Faculty of Medicine, Paris and Versailles Hospital, Paris, France; Department of Anatomy, University of Giessen, Giessen, Germany; and Department of Occupational Medicine, University of Padua, Padua, Italy

Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (~ 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, [Sar9, 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 [Sar9, 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. [Sar9, Met(O2)11]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size (~ 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar9, 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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Copyright © 2001 American Thoracic Society