Oral β-stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent and efferent nervous system via gastric β ₂-adrenoceptor stimulation

Abstract.

Objective and Design: We previously demonstrated that oral l-ephedrine exerts an extremely rapid (within 20 s) inhibition of 48-h passive cutaneous anaphylaxis reaction (PCA) in rats by a possibly unidentified mode of action. In the present experiments, we elucidated the mechanism of the PCA inhibition by l-ephedrine using adrenoceptor agonists and antagonists.¶Materials: Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis.¶Treatment: Passively skin-sensitised Wistar rats were mainly used. l-Ephedrine, and adrenoceptor agonists and antagonists were orally administered immediately before PCA provocation. Catecholamine depleting (6-hydroxydopamine, 6-OH-DA), amine depleting (reserpine) or ganglion blocking (hexamethonium) agent was intraperitoneally or intravenously administered before the provocation.¶Methods: The effects of the drugs on PCA were assessed by inhibition of the dye leakage.¶Results: β-(propranolol) and β ₂-(butoxamine) blocking agents reduced the inhibition of PCA by l-ephedrine, while the inhibition was not altered by either an α-blocking agent (phentolamine) or a β ₁-(atenolol) selective antagonist. On the other hand, β-(isoproterenol) and β ₂-selective (salbutamol) agonists showed extremely rapid inhibition of PCA. However, the β ₁-selective agonist (dobutamine) had no effect on the reaction. The pretreatment with hexamethonium, reserpine or 6-OH-DA substantially attenuated the inhibitory effect of l-ephedrine on PCA.¶Conclusions: The results strongly suggest that β ₂-adrenoceptors locate in the stomach and that their receptor excitement finally may lead to the inhibition of PCA via the stimulation of the central and peripheral nervous systems.