• M Kobayashi, H Kume, T Oguma, Y Makino, Y Ito, and K Shimokata.
• Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
• Clin. Exp. Allergy. 2008 Jan 1; 38 (1): 135-44.

BackgroundRecent studies have revealed that in asthma, mast cells infiltrate to the smooth muscle layer and release tryptase, an enzymatic activator of protease-activated receptor 2 (PAR2). This phenomenon, mast cell myositis, is proposed as a new feature of asthma. However, little is known about the involvement of mast cell myositis in the pathophysiology of asthma.ObjectiveThis study was designed to determine whether mast cell degranulation has any functional impact on beta-adrenoceptors via PAR2 in airway smooth muscle. Moreover, we focused on Ca(2+) signalling as a mechanism underlying alteration of smooth muscle tone and responsiveness.MethodsIsometric tension and F(340)/F(380), an indicator of the concentration of intracellular Ca(2+) ([Ca(2+)](i)), were simultaneously measured using fura-2-loaded tissues isolated from guinea-pig tracheal smooth muscle.ResultsTryptase (1-100 nm) caused tension with elevated F(340)/F(380), and after exposure to tryptase for 15 min the inhibitory effect of isoprenaline (ISO) against methacholine was attenuated without elevating F(340)/F(380) in a concentration-dependent manner. Tryptase (<1 nm) had a modest effect on tension, but prolonged treatment (ConclusionIn mast cell myositis, tryptase released from mast cells acts on airway smooth muscle, leading to homologous beta-adrenergic desensitization mediated by [Ca(2+)](i)-independent mechanisms via PAR2 activation.

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