[Pharmacologic modification of mediator liberation and the effect of mediators]

Blocking specific steps in the chain of events leading to disease is essential for elucidating pathogenesis. If antagonism to a given receptor does not modify the disease the receptor plays no role in the disease. In this review we describe specific points in the chain of events leading to respiratory disease at which pharmacologic intervention is possible and we describe results of such intervention. This includes interventions not presently available therapeutically. We distinguish three groups of interventions: interventions interfering with pre-receptor mechanism, those interacting with pharmacologic receptors or with proteins coupling receptor activation to cellular events and, finally, interventions affecting postreceptor mechanisms, e.g., second messenger systems including ion channels. Of the many interventions possible early pre-receptor interventions are most desirable (preventive measures), but are often not available. Interventions at the receptor level, although available and in most cases specific for a given receptor are of limited effectiveness because multiple receptor involvement predominates in respiratory disease. Interventions at the post-receptor level have been most successful thus far presumably because post receptor mechanisms (e.g. second messenger systems) are shared by many receptors, therefore interventions at this level are largely independent of receptor(s) involved and have been most effective clinically.