Immediate inhibition by oral l-ephedrine of passive cutaneous anaphylaxis of rats: indirect inhibition of anaphylactic chemical mediator release fromthe mast cell

Objective and Design: We previously reported that oral I-ephedrine showed e xtraordinarily rapid inhibition of 48-h passive cutaneous anaphylaxis (PCA) in rats. In the present study, in vivo and in vitro experiments were perfo rmed to elucidate a possible mechanism for the inhibition. Materials. Rat antiserum was prepared with dinitrophenylated Ascaris suum e xtract + Bordetella pertussis. Treatment: Wistar rats were passively skin-sensitised, actively sensitised or non-sensitised. I-Ephedrine immediately before provocations was orally o r intravenously administered in in vivo experiments. In in vitro experiment s, the drug was added at various time and concentrations before the challen ge. Methods: The intensity of PCA was assessed by dye leakage method. Histamine and serotonin released in vitro or retained in the skin in vivo by anaphyl axis were assayed fluorometrically. Results. Oral I-ephedrine rapidly inhibited the PCA by inhibiting the relea se of histamine and serotonin from the reaction site, whereas anaphylactic histamine and serotonin releases from skin fragments were not affected by t he drug. Furthermore, the orally administered drug influenced neither the h istamine- nor serotonin-induced cutaneous vascular permeability. Conclusions: These results were strongly indicative that the prompt suppres sion of the PCA by oral I-ephedrine was not exerted following the drug was absorbed from the gastrointestinal tract. Thus, the result may be from an i ndirect inhibition of chemical mediator release, possibly through an uniden tified stimulation of the nervous system, but not from the inhibition of ch emical mediator release by the direct interaction of drug to mast cells and not from the decreased vascular permeability.