Immediate inhibition by oral l-ephedrine of passive cutaneous anaphylaxis of rats: indirect inhibition of anaphylactic chemical mediator release from the mast cell.
OBJECTIVE
We previously reported that oral l-ephedrine showed extraordinarily rapid inhibition of 48-h passive cutaneous anaphylaxis (PCA) in rats. In the present study, in vivo and in vitro experiments were performed to elucidate a possible mechanism for the inhibition.


METHODS
Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis.


METHODS
Wistar rats were passively skin-sensitised, actively sensitised or non-sensitised. l-Ephedrine immediately before provocations was orally or intravenously administered in in vivo experiments. In in vitro experiments, the drug was added at various time and concentrations before the challenge.


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 anaphylaxis were assayed fluorometrically.


RESULTS
Oral l-ephedrine rapidly inhibited the PCA by inhibiting the release of histamine and serotonin from the reaction site, whereas anaphylactic histamine and serotonin releases from skin fragments were not affected by the drug. Furthermore, the orally administered drug influenced neither the histamine- nor serotonin-induced cutaneous vascular permeability.


CONCLUSIONS
These results were strongly indicative that the prompt suppression of the PCA by oral l-ephedrine was not exerted following the drug was absorbed from the gastrointestinal tract. Thus, the result may be from an indirect inhibition of chemical mediator release, possibly through an unidentified stimulation of the nervous system, but not from the inhibition of chemical mediator release by the direct interaction of drug to mast cells and not from the decreased vascular permeability.
Shibata
H
H
Central Research Laboratory, Kotaro Pharmaceutical Co. Ltd., Takatsuki, Osaka, Japan.
Minami
E
E
Hirata
R
R
Mizutani
N
N
Nabe
T
T
Kohno
S
S
D000284:Administration, Oral; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004809:Ephedrine / Q000494:pharmacology*; D006632:Histamine / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*
D012701:Serotonin; D006632:Histamine; D004809:Ephedrine