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Interleukin-1-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway.

Authors
Wu-ZX; Satterfield-BE; Fedan-JS; Dey-RD
Source
Am J Physiol, Lung Cell Mol Physiol 2002 Nov; 283(5):L909-L917
NIOSHTIC No.
20022832
Abstract
Interleukin (IL)-1 causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1. Ferrets were instilled intratracheally with IL-1 (0.3 g/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1. The IL-1-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1. These results show that IL-1-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.
Keywords
Animal-studies; Animals; Muscles; Muscular-disorders; Laboratory-animals; In-vitro-study; Electrical-stimulation; Author Keywords: airway inflammation; airway smooth muscle contraction; muscarinic agonists; neurokinin receptor; airway innervation
Contact
R.D. Dey, Dept. of Neurobiology and Anatomy, PO Box 9128, West Virginia Univ., Morgantown, WV 26506
CODEN
APLPE7
Publication Date
20021101
Document Type
Journal Article
Email Address
rdey@hsc.wvu.edu
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
1040-0605
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
WV
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