Oral beta-stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent andefferent nervous system via gastric beta(2)-adrenoceptor stimulation

Objective and Design: We previously demonstrated that oral l-ephedrine exer ts an extremely rapid (within 20 s) inhibition of 48-h passive cutaneous an aphylaxis reaction (PCA) in rats by a possibly unidentified mode of action. In the present experiments, we elucidated the mechanism of the PCA inhibit ion by l-ephedrine using adrenoceptor agonists and antagonists. Materials: Rat antiserum was prepared with dinitrophenylated Ascaris suum e xtract + Bordetella pertussis. Treatment: Passively skin-sensitised Wistar rats were mainly used. l-ephedr ine, and adrenoceptor agonists and antagonists were orally administered imm ediately before PCA provocation. Catecholamine depleting (6-hydroxydopamine , 6-OHDA), amine depleting (reserpine) or ganglion blocking (hexamethonium) agent was intraperitoneally or intravenously administered before the provo cation. Methods: The effects of the drugs on PCA were assessed by inhibition of the dye leakage. Results: beta-(propranolol) and beta (2)-(butoxamine) blocking agents reduc ed the inhibition of PCA by l-ephedrine, while the inhibition was not alter ed by either an alpha -blocking agent (phentolamine) or a beta (1)-(atenolo l) selective antagonist. On the other hand, beta-(isoproterenol) and beta ( 2)-selective (salbutamol) agonists showed extremely rapid inhibition of PCA . However, the Pi-selective agonist (dobutamine) had no effect on the react ion. The pretreatment with hexamethonium, reserpine or 6-OH-DA substantiall y attenuated the inhibitory effect of l-ephedrine on PCA. Conclusions: The results strongly suggest that beta (2)-adrenoceptors locat e in the stomach and that their receptor excitement finally may lead to the inhibition of PCA via the stimulation of the central and peripheral nervou s systems.