IMR Press / FBL / Volume 15 / Issue 2 / DOI: 10.2741/3644

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Mechanisms of airway smooth muscle relaxation induced by beta2-adrenergic agonists
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1 Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Academic Editor:Reynold Panettieri
Front. Biosci. (Landmark Ed) 2010, 15(2), 750–764;
Published: 1 January 2010
(This article belongs to the Special Issue Beta2 agonists in airways disease: molecules to medicine)

Airway smooth muscle cell (ASMC) contraction is regulated by myosin phosphorylation to control actin-myosin cross-bridge activity. Myosin phosphorylation is determined by the antagonistic activity of myosin light chain (MLC) kinase (MLCK) and phosphatase (MLCP). MLCK activity is increased by increases in intracellular Ca2+ concentration ([Ca2+]i) associated with Ca2+ oscillations. MLCP activity is decreased by phosphorylation of MLCP or accessory proteins by kinases, including Rho-kinase or protein kinase C. During agonist-induced ASMC contraction, these 2 pathways are simultaneously activated. Because MLCP activity is often independent of [Ca2+]i, changes in MLCP activity can alter ASMC tone at a constant [Ca2+]i; a behavior termed Ca2+ sensitivity. In asthma, airway hyperresponsiveness (AHR) may result from an increase in the Ca2+-dependent contractile mechanisms and/or the Ca2+ sensitivity of ASMCs. Conversely, inhalation of beta2-adrenergic agonists induce airway relaxation by simultaneously slowing the Ca2+ oscillations and reducing the Ca2+ sensitivity of ASMCs. However, the action of beta2-adrenergic agonists varies with species. Consequently, the development of beta2-adrenergic agonists requires a characterization of their action in human airways.

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