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U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release.
Am J Respir Crit Care Med. 1995 Feb; 151(2 Pt 1):321-4.AJ

Abstract

Thromboxane A2 (TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. U46619 is a chemical that mimics the effects of TxA2. Both TxA2 and U46619 have been demonstrated to act presynaptically to enhance the release of acetylcholine from cholinergic nerves in canine airway smooth muscle. The purpose of this study was to determine whether the bronchoconstriction caused by inhaled U46619 in asthmatic subjects is caused by acetylcholine release. Airway responsiveness to inhaled methacholine and U46619 was measured in eight subjects with mild stable asthma and expressed as the provocation concentration causing a 20% fall in FEV1 (PC20). Subjects were studied on 4 d, each separated by 3 days. On each study day, subjects inhaled a cholinergic antagonist ipratropium bromide (80 micrograms), or placebo, and 1 h later, increasing doubling doses of methacholine or U46619 were inhaled, and a PC20 value was obtained. The mean methacholine PC20 on the placebo day was 1.42 mg/ml (%SEM, 1.47) and after treatment with ipratropium bromide this increased to 127.33 mg/ml (%SEM, 1.29) (p = 0.0001), a mean 89.4-fold (%SEM, 1.19) increase. The mean U46619 PC20 on the placebo day was 2.09 micrograms/ml (%SEM, 1.56) and after treatment with ipratropium bromide this increased to 47.54 micrograms/ml (%SEM, 1.43) (p = 0.0001), a mean 22.8-fold (%SEM, 1.36) increase. The ability of ipratropium bromide to attenuate responsiveness to the noncholinergic mediator histamine was also investigated in six subjects. The mean increase in histamine PC20 was a 3.09-fold (%SEM, 1.17) increase, significantly less than the increase seen for both methacholine and U46619 (p < 0.001).(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7842185

Citation

Saroea, H G., et al. "U46619-induced Bronchoconstriction in Asthmatic Subjects Is Mediated By Acetylcholine Release." American Journal of Respiratory and Critical Care Medicine, vol. 151, no. 2 Pt 1, 1995, pp. 321-4.
Saroea HG, Inman MD, O'Byrne PM. U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release. Am J Respir Crit Care Med. 1995;151(2 Pt 1):321-4.
Saroea, H. G., Inman, M. D., & O'Byrne, P. M. (1995). U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release. American Journal of Respiratory and Critical Care Medicine, 151(2 Pt 1), 321-4.
Saroea HG, Inman MD, O'Byrne PM. U46619-induced Bronchoconstriction in Asthmatic Subjects Is Mediated By Acetylcholine Release. Am J Respir Crit Care Med. 1995;151(2 Pt 1):321-4. PubMed PMID: 7842185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release. AU - Saroea,H G, AU - Inman,M D, AU - O'Byrne,P M, PY - 1995/2/1/pubmed PY - 1995/2/1/medline PY - 1995/2/1/entrez SP - 321 EP - 4 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 151 IS - 2 Pt 1 N2 - Thromboxane A2 (TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. U46619 is a chemical that mimics the effects of TxA2. Both TxA2 and U46619 have been demonstrated to act presynaptically to enhance the release of acetylcholine from cholinergic nerves in canine airway smooth muscle. The purpose of this study was to determine whether the bronchoconstriction caused by inhaled U46619 in asthmatic subjects is caused by acetylcholine release. Airway responsiveness to inhaled methacholine and U46619 was measured in eight subjects with mild stable asthma and expressed as the provocation concentration causing a 20% fall in FEV1 (PC20). Subjects were studied on 4 d, each separated by 3 days. On each study day, subjects inhaled a cholinergic antagonist ipratropium bromide (80 micrograms), or placebo, and 1 h later, increasing doubling doses of methacholine or U46619 were inhaled, and a PC20 value was obtained. The mean methacholine PC20 on the placebo day was 1.42 mg/ml (%SEM, 1.47) and after treatment with ipratropium bromide this increased to 127.33 mg/ml (%SEM, 1.29) (p = 0.0001), a mean 89.4-fold (%SEM, 1.19) increase. The mean U46619 PC20 on the placebo day was 2.09 micrograms/ml (%SEM, 1.56) and after treatment with ipratropium bromide this increased to 47.54 micrograms/ml (%SEM, 1.43) (p = 0.0001), a mean 22.8-fold (%SEM, 1.36) increase. The ability of ipratropium bromide to attenuate responsiveness to the noncholinergic mediator histamine was also investigated in six subjects. The mean increase in histamine PC20 was a 3.09-fold (%SEM, 1.17) increase, significantly less than the increase seen for both methacholine and U46619 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/7842185/U46619_induced_bronchoconstriction_in_asthmatic_subjects_is_mediated_by_acetylcholine_release_ L2 - https://www.atsjournals.org/doi/10.1164/ajrccm.151.2.7842185?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -