H. Jiang et al., EARLY CHANGES IN AIRWAY SMOOTH-MUSCLE HYPERRESPONSIVENESS, Canadian journal of physiology and pharmacology, 72(11), 1994, pp. 1440-1447
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.