Endogenous regulation of bronchomotor tone

Airway smooth muscle responses are elicited in a complex manner through a large variety of endogenous mediators. Mediators augment or inhibit bronchomotor tone at a variety of sites through numerous different mechanisms. Interactions occur among mediators and nerves, muscle, and circulating blood elements or respiratory mast cells. Airway smooth muscle tone further is regulated by postsynaptic mediator-mediator interactions. Substances may circulate through the blood from distal sites to reach their target organ, as with epinephrine in its effects on airway smooth muscle, or may be secreted directly onto airway smooth muscle, as with the secretory products of respiratory mast cells. Recent observations have indicated that some mediators elicit airway contraction at least in part by activating efferent parasympathetic nerves and/or platelets. Direct secretion of minute quantities of mediators from adjacent epithelium or from infiltrating leukocytes may be an essential component of airway hyperreactivity. Complex interactions between the complement and kallikrein cascades have been cited as possible mechanisms of airway hyperresponsiveness. Ultimately, bronchomotor tone is mediated postsynaptically by the availability of calcium to the contractile apparatus of the smooth muscle cell. A role for the phosphoinositide system in membrane transduction and for cyclic adenosine monophosphate in regulating calcium distribution for smooth muscle contraction has been implicated. Mediator-mediator interactions distal to the synaptic cleft have been shown to augment both force and duration of airway smooth muscle contraction in a synergistic fashion. The stimuli eliciting mediator and neurotransmitter secretion, their physiologic significance, and the homeostatic infrastructure of these interactions are areas of promising investigation that require further definition.