Sensitization to anaphylaxis and to some of its pharmacological mediators by blockade of the beta adrenergic receptors

Strain differences are described in the hypersensitivity to anaphylaxis, and to some of its pharmacologic mediators, produced by pertussis or blockade of the beta-adrenergic receptors. Thus, pertussis did not produce histamine hypersensitivity in CF₁ but did in CFW mice; in contrast, pertussis produced methacholine hypersensitivity in CF₁ but not in CFW mice. Blockade of beta receptors with dichloroiso-proterenol (DCI), Nethalide, or MJ-1999 sensitized both CFW and CF₁ mice to histamine, but the hypersensitivity was greater in CFW, followed by CF₁, and finally by nonobese siblings of "obese-hyperglycemic" mice. This relationship was paralleled by that of the natural histamine-sensitivity of the three strains. A bimodal response to histamine was found in untreated CFW mice, but only after beta blockade in CF₁ mice. In general, MJ-1999 was the most and DCI the least potent sensitizer, with Nethalide showing intermediate activity. MJ-1999 produced hypersensitivity to the amines in Hartley, but not in Trapani-Campbell, guinea pigs. Both blocked strains could be sensitized, however, to anaphylaxis. Interventions conceivably resulting in additive blockade of beta or simultaneous stimulation of alpha receptors could break strain resistance to sensitization. Conversely, protection of susceptible strains was obtained through procedures known to protect beta receptors against development of a blockade, or to by-pass or eliminate an already-established blockade. While alpha blockers did not show sensitizing activity, such properties of beta blockers were shown to be unrelated to some of their nonspecific (i.e., histamine-releasing) effects. Likewise, no correlation was found between the antihistaminic-antiserotonin and the protective activities of alpha blockers against pertussis-induced hypersensitivity. These findings were interpreted to mean that the sensitizing activity of the beta adrenergic blocking agents is due to their ability to inhibit the beta pharmacological actions of the adrenergic neurotransmitters or those of their exogenous counterparts.