Am. J. Respir. Crit. Care Med., Volume 161, Number 1, January 2000, 207-215

The Distribution of Neurokinin-1 and Neurokinin-2 Receptors in Human Central Airways

CRISTINA E. MAPP, DEBORAH MIOTTO, FAUSTO BRACCIONI, MARINA SAETTA, GRAZIELLA TURATO, PIERO MAESTRELLI, JAMES E. KRAUSE, VLADIMIR KARPITSKIY, NORMAN BOYD, PIERO GEPPETTI, and LEONARDO M. FABBRI

Institute of Occupational Medicine, University of Padua, Padua, Italy; Section of Biochemistry, Neurogen, Inc., Branford, Connecticut; Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts; and Research Centre on Asthma and COPD, and Section of Pharmacology, Department of Experimental and Clinical Medicine, University of Ferrara, Ferrara, Italy

The precise locations of neurokinin (NK)-1 and NK-2 receptors in human airways, and their role in airway inflammatory diseases, have not been carefully examined. To determine the distribution of NK-1 and NK-2 receptors in human central airways, and to determine whether their distribution was different in smokers, we examined surgical specimens from patients undergoing lung resection for limited lung lesions. We mapped NK-1 and NK-2 receptors in four groups of subjects: four asymptomatic nonsmokers, seven asymptomatic smokers, seven symptomatic smokers with normal lung function, and eight symptomatic smokers with chronic airflow limitation. Tissues were immunostained with anti-NK-1- and anti-NK-2-receptor antibodies. Expression of NK-1 and NK-2 receptors was quantified through light microscopy and image analysis. Both NK-1 and NK-2 receptors were found in bronchial glands, bronchial vessels, and bronchial smooth muscle. Although no receptors were observed in the epithelium, receptors were occasionally found in nerves (NK-1) and in inflammatory cells (NK-2) such as T lymphocytes, macrophages, and mast cells. The distribution of both NK-1 and NK-2 receptors was similar in all the tissues examined in the four groups of subjects. These data show that NK-1 and NK-2 receptors are present in human central airways and that their expression is not modified by cigarette smoking. Mapp CE, Miotto D, Braccioni F, Saetta M, Turato G, Maestrelli P, Krause JE, Karpitskiy V, Boyd N, Geppetti P, Fabbri LM. The distribution of neurokinin-1 and neurokinin-2 receptors in human central airways.

This article has been cited by other articles:

				K. Mizuta, G. Gallos, D. Zhu, F. Mizuta, F. Goubaeva, D. Xu, R. A. Panettieri Jr., J. Yang, and C. W. Emala Sr. Expression and coupling of neurokinin receptor subtypes to inositol phosphate and calcium signaling pathways in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L523 - L534. [Abstract] [Full Text] [PDF]

				E. D. Zee, S. Schomberg, and T. C. Carpenter Hypoxia upregulates lung microvascular neurokinin-1 receptor expression Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L102 - L110. [Abstract] [Full Text] [PDF]

				P. J. Barnes Distribution of Receptor Targets in the Lung Proceedings of the ATS, December 1, 2004; 1(4): 345 - 351. [Abstract] [Full Text] [PDF]

				P. J. Barnes Mediators of Chronic Obstructive Pulmonary Disease Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548. [Abstract] [Full Text] [PDF]

				R. A. Joachim, V. Sagach, D. Quarcoo, Q. T. Dinh, P. C. Arck, and B. F. Klapp Neurokinin-1 Receptor Mediates Stress-Exacerbated Allergic Airway Inflammation and Airway Hyperresponsiveness in Mice Psychosom Med, July 1, 2004; 66(4): 564 - 571. [Abstract] [Full Text] [PDF]

				G.F. Joos, W. Vincken, R. Louis, V.J. Schelfhout, J.H. Wang, M.J. Shaw, G.D. Cioppa, and R.A. Pauwels Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients Eur. Respir. J., January 1, 2004; 23(1): 76 - 81. [Abstract] [Full Text] [PDF]

				B. Grubor, R. Ramirez-Romero, J. M. Gallup, T. B. Bailey, and M. R. Ackermann Distribution of Substance P Receptor (Neurokinin-1 Receptor) in Normal Ovine Lung and During the Progression of Bronchopneumonia in Sheep J. Histochem. Cytochem., January 1, 2004; 52(1): 123 - 130. [Abstract] [Full Text] [PDF]

				A. N. Freed, S. McCulloch, T. Meyers, and R. Suzuki Neurokinins Modulate Hyperventilation-induced Bronchoconstriction in Canine Peripheral Airways Am. J. Respir. Crit. Care Med., April 15, 2003; 167(8): 1102 - 1108. [Abstract] [Full Text] [PDF]

				K.G. Tournoy, K.O. De Swert, P.G. Leclere, R.A. Lefebvre, R.A. Pauwels, and G.F. Joos Modulatory role of tachykinin NK1 receptor in cholinergic contraction of mouse trachea Eur. Respir. J., January 1, 2003; 21(1): 3 - 10. [Abstract] [Full Text] [PDF]

				K. Maghni, M.-C. Michoud, M. Alles, A. Rubin, V. Govindaraju, C. Meloche, and J. G. Martin Airway Smooth Muscle Cells Express Functional Neurokinin-1 Receptors and the Nerve-Derived Preprotachykinin-A Gene: Regulation by Passive Sensitization Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 103 - 110. [Abstract] [Full Text] [PDF]

				S. S Wong, N. N Sun, R C. Lantz, and M. L Witten Tissue-specific patterns of neurokinin-1 receptor (NK-1R) gene expression in mice exposed to sidestream cigarette smoke Toxicology and Industrial Health, October 1, 2002; 18(9-10): 435 - 444. [Abstract] [PDF]

				J. Van Schoor, G.F. Joos, and R.A. Pauwels Effect of inhaled fluticasone on bronchial responsiveness to neurokinin A in asthma Eur. Respir. J., June 1, 2002; 19(6): 997 - 1002. [Abstract] [Full Text] [PDF]

				E. L. J. Van Rensen, P. S. Hiemstra, K. F. Rabe, and P. J. Sterk Assessment of Microvascular Leakage via Sputum Induction: The Role of Substance P and Neurokinin A in Patients with Asthma Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1275 - 1279. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2000 Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1789 - 1804. [Full Text] [PDF]

				F. SCHMIDLIN, S. AMADESI, R. VIDIL, M. TREVISANI, N. MARTINET, G. CAUGHEY, M. TOGNETTO, G. CAVALLESCO, C. MAPP, P. GEPPETTI, et al. Expression and Function of Proteinase-activated Receptor 2 in Human Bronchial Smooth Muscle Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1276 - 1281. [Abstract] [Full Text] [PDF]

				S. AMADESI, J. MOREAU, M. TOGNETTO, J. SPRINGER, M. TREVISANI, E. NALINE, C. ADVENIER, A. FISHER, D. VINCI, C. MAPP, et al. NK1 Receptor Stimulation Causes Contraction and Inositol Phosphate Increase in Medium-size Human Isolated Bronchi Am. J. Respir. Crit. Care Med., April 1, 2001; 163(5): 1206 - 1211. [Abstract] [Full Text]