Tags

Type your tag names separated by a space and hit enter

Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism.
Am J Physiol Lung Cell Mol Physiol. 2006 Mar; 290(3):L526-33.AJ

Abstract

Thromboxane A2 (TXA2) is a potent lipid mediator released by platelets and inflammatory cells and is capable of inducing vasoconstriction and bronchoconstriction. In the airways, it has been postulated that TXA2 causes airway constriction by direct activation of thromboxane prostanoid (TP) receptors on airway smooth muscle cells. Here we demonstrate that although TXA2 can mediate a dramatic increase in airway smooth muscle constriction and lung resistance, this response is largely dependent on vagal innervation of the airways and is highly sensitive to muscarinic acetylcholine receptor (mAChR) antagonists. Further analyses employing pharmacological and genetic strategies demonstrate that TP-dependent changes in lung resistance and airway smooth muscle tension require expression of the M2 mAChR subtype. These results raise the possibility that some of the beneficial actions of anticholinergic agents used in the treatment of asthma and chronic obstructive pulmonary disease result from limiting physiological changes mediated through the TP receptor. Furthermore, these findings demonstrate a unique pathway for TP regulation of homeostatic mechanisms in the airway and suggest a paradigm for the role of TXA2 in other organ systems.

Authors+Show Affiliations

Curriculum in Genetics and Molecular Biology, Univ. of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16243899

Citation

Allen, Irving C., et al. "Thromboxane A2 Induces Airway Constriction Through an M3 Muscarinic Acetylcholine Receptor-dependent Mechanism." American Journal of Physiology. Lung Cellular and Molecular Physiology, vol. 290, no. 3, 2006, pp. L526-33.
Allen IC, Hartney JM, Coffman TM, et al. Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism. Am J Physiol Lung Cell Mol Physiol. 2006;290(3):L526-33.
Allen, I. C., Hartney, J. M., Coffman, T. M., Penn, R. B., Wess, J., & Koller, B. H. (2006). Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism. American Journal of Physiology. Lung Cellular and Molecular Physiology, 290(3), L526-33.
Allen IC, et al. Thromboxane A2 Induces Airway Constriction Through an M3 Muscarinic Acetylcholine Receptor-dependent Mechanism. Am J Physiol Lung Cell Mol Physiol. 2006;290(3):L526-33. PubMed PMID: 16243899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism. AU - Allen,Irving C, AU - Hartney,John M, AU - Coffman,Thomas M, AU - Penn,Raymond B, AU - Wess,Jürgen, AU - Koller,Beverly H, Y1 - 2005/10/21/ PY - 2005/10/26/pubmed PY - 2006/3/22/medline PY - 2005/10/26/entrez SP - L526 EP - 33 JF - American journal of physiology. Lung cellular and molecular physiology JO - Am. J. Physiol. Lung Cell Mol. Physiol. VL - 290 IS - 3 N2 - Thromboxane A2 (TXA2) is a potent lipid mediator released by platelets and inflammatory cells and is capable of inducing vasoconstriction and bronchoconstriction. In the airways, it has been postulated that TXA2 causes airway constriction by direct activation of thromboxane prostanoid (TP) receptors on airway smooth muscle cells. Here we demonstrate that although TXA2 can mediate a dramatic increase in airway smooth muscle constriction and lung resistance, this response is largely dependent on vagal innervation of the airways and is highly sensitive to muscarinic acetylcholine receptor (mAChR) antagonists. Further analyses employing pharmacological and genetic strategies demonstrate that TP-dependent changes in lung resistance and airway smooth muscle tension require expression of the M2 mAChR subtype. These results raise the possibility that some of the beneficial actions of anticholinergic agents used in the treatment of asthma and chronic obstructive pulmonary disease result from limiting physiological changes mediated through the TP receptor. Furthermore, these findings demonstrate a unique pathway for TP regulation of homeostatic mechanisms in the airway and suggest a paradigm for the role of TXA2 in other organ systems. SN - 1040-0605 UR - https://www.unboundmedicine.com/medline/citation/16243899/Thromboxane_A2_induces_airway_constriction_through_an_M3_muscarinic_acetylcholine_receptor_dependent_mechanism_ L2 - http://journals.physiology.org/doi/full/10.1152/ajplung.00340.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -