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Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine.
Am Rev Respir Dis. 1990 Nov; 142(5):1112-8.AR

Abstract

Airways responsiveness to leukotriene (LT) C4, LTD4, LTE4, histamine, and methacholine have been studied in eight asthmatic and six normal subjects. Airways responsiveness to each bronchoconstrictor agonist was assessed by constructing cumulative dose-response curves, and the dose that produced a 35% decrease in specific airways conductance (PD35) was obtained by linear interpolation. Airways of subjects with asthma were approximately 14-, 15-, 6-, 9-, and 219-fold more responsive to histamine, methacholine, LTC4, LTD4, and LTE4, respectively, than were normal subjects. Thus, there was a substantially augmented level of hyperresponsiveness to LTE4 in bronchial asthma, which was not observed for the other bronchoconstrictor agents, when compared to normal subjects. In contrast to LTC4 and LTD4, as histamine and methacholine responsiveness increase, the dose ratio of histamine to LTE4 (PD35 histamine/PD35 LTE4) and the dose ratio of methacholine to LTE4 also tended to increase. This suggests that as the nonspecific airways responsiveness increases, the relative potency of LTE4 also increases, whereas potency of LTC4 and LTD4 decrease. These results suggest that the mechanism of the bronchoconstriction induced by LTE4 may be distinct from that produced by LTC4 or LTD4 in subjects with asthma. This may reflect leukotriene subtype receptor heterogeneity in asthmatic airways.

Authors+Show Affiliations

Department of Allergy and Allied Respiratory Disorders, U.M.D.S., Guy's Hospital, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2173457

Citation

Arm, J P., et al. "Asthmatic Airways Have a Disproportionate Hyperresponsiveness to LTE4, as Compared With Normal Airways, but Not to LTC4, LTD4, Methacholine, and Histamine." The American Review of Respiratory Disease, vol. 142, no. 5, 1990, pp. 1112-8.
Arm JP, O'Hickey SP, Hawksworth RJ, et al. Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine. Am Rev Respir Dis. 1990;142(5):1112-8.
Arm, J. P., O'Hickey, S. P., Hawksworth, R. J., Fong, C. Y., Crea, A. E., Spur, B. W., & Lee, T. H. (1990). Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine. The American Review of Respiratory Disease, 142(5), 1112-8.
Arm JP, et al. Asthmatic Airways Have a Disproportionate Hyperresponsiveness to LTE4, as Compared With Normal Airways, but Not to LTC4, LTD4, Methacholine, and Histamine. Am Rev Respir Dis. 1990;142(5):1112-8. PubMed PMID: 2173457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine. AU - Arm,J P, AU - O'Hickey,S P, AU - Hawksworth,R J, AU - Fong,C Y, AU - Crea,A E, AU - Spur,B W, AU - Lee,T H, PY - 1990/11/1/pubmed PY - 1990/11/1/medline PY - 1990/11/1/entrez SP - 1112 EP - 8 JF - The American review of respiratory disease JO - Am Rev Respir Dis VL - 142 IS - 5 N2 - Airways responsiveness to leukotriene (LT) C4, LTD4, LTE4, histamine, and methacholine have been studied in eight asthmatic and six normal subjects. Airways responsiveness to each bronchoconstrictor agonist was assessed by constructing cumulative dose-response curves, and the dose that produced a 35% decrease in specific airways conductance (PD35) was obtained by linear interpolation. Airways of subjects with asthma were approximately 14-, 15-, 6-, 9-, and 219-fold more responsive to histamine, methacholine, LTC4, LTD4, and LTE4, respectively, than were normal subjects. Thus, there was a substantially augmented level of hyperresponsiveness to LTE4 in bronchial asthma, which was not observed for the other bronchoconstrictor agents, when compared to normal subjects. In contrast to LTC4 and LTD4, as histamine and methacholine responsiveness increase, the dose ratio of histamine to LTE4 (PD35 histamine/PD35 LTE4) and the dose ratio of methacholine to LTE4 also tended to increase. This suggests that as the nonspecific airways responsiveness increases, the relative potency of LTE4 also increases, whereas potency of LTC4 and LTD4 decrease. These results suggest that the mechanism of the bronchoconstriction induced by LTE4 may be distinct from that produced by LTC4 or LTD4 in subjects with asthma. This may reflect leukotriene subtype receptor heterogeneity in asthmatic airways. SN - 0003-0805 UR - https://www.unboundmedicine.com/medline/citation/2173457/Asthmatic_airways_have_a_disproportionate_hyperresponsiveness_to_LTE4_as_compared_with_normal_airways_but_not_to_LTC4_LTD4_methacholine_and_histamine_ L2 - https://www.atsjournals.org/doi/10.1164/ajrccm/142.5.1112?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -