Inflammatory mediator receptors and asthma.

Many inflammatory mediators (histamine, prostanoids, leukotrienes, platelet-activating factor, adenosine, bradykinin, and sensory neuropeptides) have been implicated in the pathogenesis of asthma and produce their effects by activating specific cell surface receptors. Activation of these receptors may result in contraction of airway smooth muscle, mucus and fluid secretion, microvascular leakiness, chemotaxis of inflammatory cells, and neuronal activation, indicating that the receptors are localized to a variety of cells. Recent studies have indicated that mediator receptor activation may lead to a response either by modulating adenylate cyclase or by stimulating breakdown of membrane phosphoinositides, which release intracellular calcium ions. The latter mechanism appears to predominate, at least in the case of airway smooth muscle receptors. Several receptors for inflammatory mediators have been characterized functionally and by direct receptor binding techniques, and receptor subtypes have been recognized. Several specific mediator receptor antagonists have been developed but are unlikely to have a major clinical effect because so many different mediators are likely to contribute to the pathology of asthma. Platelet-activating factor, possibly by acting on specific platelet receptors, is able to increase nonspecific bronchial responsiveness in human subjects, so it is possible that specific receptor antagonists of this phospholipid mediator might reduce the enhanced responsiveness to other inflammatory mediators which occurs in asthma.