EARLY CHANGES IN AIRWAY SMOOTH-MUSCLE HYPERRESPONSIVENESS

Citation
H. Jiang et al., EARLY CHANGES IN AIRWAY SMOOTH-MUSCLE HYPERRESPONSIVENESS, Canadian journal of physiology and pharmacology, 72(11), 1994, pp. 1440-1447
Citations number
34
Categorie Soggetti
Pharmacology & Pharmacy",Physiology
ISSN journal
00084212
Volume
72
Issue
11
Year of publication
1994
Pages
1440 - 1447
Database
ISI
SICI code
0008-4212(1994)72:11<1440:ECIASH>2.0.ZU;2-7
Abstract
To study asthmatic airway smooth muscle we developed a canine model of ragweed pollen sensitized, airway hyperresponsiveness because of the difficulties in obtaining human tissue. Tracheal and bronchial smooth muscles from sensitized dogs were shown to possess greater ability to shorten and higher maximum shortening velocity (V-o), both of which co ntribute to the excessive narrowing of airways typical of human asthma . However, maximum force production remained normal, demonstrating the dissociation between the behaviour of shortening and force. Because w e found no evidence of inflammation, hypertrophy, or hyperplasia in th e sensitized airway smooth muscles, we felt this is a model of early d isease and should provide insight into early and perhaps primary patho genetic mechanisms. V-o is known to be determined by actomyosin ATPase , which in smooth muscle is activated via phosphorylation of the 20-kD a myosin light chain (MLC(20)) by myosin light chain kinase (MLCK). Th erefore, ATPase activity, MLC(20) phosphorylation, and MLCK were inves tigated. Sensitized tracheal and bronchial smooth muscles showed signi ficantly higher ATPase activity, and a higher level of MLC(20), phosph orylation, resulting from increased MLCK activity, a consequence of th e measured increase in total quantity of MLCK rather than in specific activity. Since MLCK is activated by binding with Ca2+-calmodulin comp lex, intracellular Ca2+ concentration and calmodulin activity were als o assessed, but no difference was found between sensitized and control animals. Our study suggests that increased MLCK quantity may be the c ause of airway hyperresponsiveness found in sensitized animals, and fu ture investigation should be focused on depicting the reason for the e levated MLCK.