In vitro sensitization of human bronchus by beta2-adrenergic agonists

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 27; no. 5; p. L1033
• Main Authors: Faisy, Christophe, Naline, Emmanuel, Diehl, Jean-Luc, Emonds-Alt, Xavier
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.11.2002
• Subjects: Asthma; Respiratory system
• ISSN: 1040-0605; 1522-1504

Incubation of human distal bronchi from 48 patients for 15 h with 10(-7) M fenoterol induced sensitization characterized by an increase in maximal contraction to endothelin-1 (ET-1) and acetylcholine (ACh). Incubation of human bronchi with 10(-6), 3 × 10(-6), and 10(-5) M forskolin (an adenyl cyclase activator) reproduced sensitization to ET-1 and ACh. The sensitizing effect of fenoterol was inhibited by coincubation with gliotoxine (a nuclear factor-B inhibitor), dexamethasone, indomethacin (a cyclooxygenase inhibitor), GR-32191 (a TP prostanoid receptor antagonist), MK-476 (a cysteinyl leukotriene type 1 receptor antagonist), SR-140333 + SR-48968 + SR-142801 (neurokinin types 1, 2, and 3 tachykinin receptor antagonists) with or without HOE-140 (a bradykinin B2 receptor antagonist), SB-203580 (an inhibitor of the 38-kDa mitogen-activated protein kinase, p38MAPK), or calphostin C (a protein kinase C blocker). Our results suggest that chronic exposure to fenoterol induces proinflammatory effects mediated by nuclear factor-B and pathways involving leukotrienes, prostanoids, bradykinin, tachykinins, protein kinase C, and p38MAPK, leading to the regulation of smooth muscle contraction to ET-1 and ACh.