[Molecular mechanisms of the hyperresponsiveness of airway smooth muscle in bronchial asthma].
Nonspecific airway hyperresponsiveness (AHR) is a common feature of allergic bronchial asthmatics, but the underlying mechanisms of AHR have yet to be elucidated. The importance of AHR in the pathogenesis of asthma has been suggested by its relevance to the severity of this disease. There is thus a need to understand the underlying mechanisms of AHR for the sake of asthma therapy. In allergic asthmatics, airway smooth muscles (ASMs) obtained from in vivo hyperresponsive patients have in vitro hyperresponsiveness to cholinergic agonists. It is therefore possible that the mechanisms responsible for the AHR exist, at least in part, on the ASM site. Although ASM is known to contract in response to acetylcholine via muscarinic M3 receptors and this contractile response is augmented during AHR, no alteration in muscarinic receptor density in ASM has been demonstrated in various AHR models. It is thus likely that augmented intracellular signaling might be a possible reason for the AHR. In fact, recent investigations demonstrated increases in the levels of GTP binding protein, Ca2+ mobilization and inositol 1,4,5-trisphosphate generation and so on in hyperresponsive ASM.
Chiba
Y
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Misawa
M
M
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D009130:Muscle, Smooth / Q000503:physiopathology; D011976:Receptors, Muscarinic / Q000032:analysis; D015398:Signal Transduction
D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D002118:Calcium