Role of calcium in airway smooth muscle contraction and mast cell secretion.
The principal pathological features of asthma, including tracheobronchial smooth muscle contraction and mast cell mediator synthesis and release, are calcium-dependent processes. Calcium plays an integral role in transmitting signals at the cell surface to the enzymatic machinery of the cell interior; its role as the agent for "excitation-contraction coupling" of airway smooth muscle and for "stimulus-secretion coupling" of mast cells is reviewed. A rise in intracellular calcium ion concentration triggers cellular activation. In smooth muscle, calcium bound to calmodulin stimulates the myosin light chain kinase which is important in the regulation of actin-myosin interaction. In mast cells, calcium may bind to calmodulin or to a calmodulinlike regulatory protein, and it also stimulates enzymes important in the synthesis of newly generated mediators including prostaglandins and leukotrienes. The regulatory role of cyclic AMP in both cell systems is discussed, especially as it pertains to calcium metabolism. By interfering with transmembrane calcium fluxes, the calcium channel blocking drugs have the potential for significantly modifying bronchoconstriction and airway inflammation in asthma and related bronchospastic disorders. Some of the in vitro studies of calcium channel blockers in these two cell systems are reviewed. Finally a speculation about the role of abnormal sensitivity to calcium in airway smooth muscle as a potential cause of airway hyperreactivity is entertained.
D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001980:Bronchi / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002630:Chemotactic Factors / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D014132:Trachea / Q000378:metabolism / Q000503:physiopathology*
D002121:Calcium Channel Blockers; D002630:Chemotactic Factors; D002118:Calcium