Oral beta-stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent and efferent nervous system via gastric beta2-adrenoceptor stimulation.
OBJECTIVE
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.


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


METHODS
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-OHDA), 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
beta-(propranolol) and beta2-(butoxamine) blocking agents reduced the inhibition of PCA by l-ephedrine, while the inhibition was not altered by either an a-blocking agent (phentolamine) or a beta1-(atenolol) selective antagonist. On the other hand, beta-(isoproterenol) and beta2-selective (salbutamol) agonists showed extremely rapid inhibition of PCA. However, the beta-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 beta2-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.
Shibata
H
H
Central Research Laboratory, Kotaro Pharmaceutical Co. Ltd., Takatsuki, Osaka, Japan.
Minami
E
E
Hirata
R
R
Nabe
T
T
Kohno
S
S
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D004809:Ephedrine / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009476:Neurons, Efferent / Q000187:drug effects*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000294:innervation*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D015259:Dopamine Agents; D006584:Hexamethonium Compounds; D004809:Ephedrine; D007545:Isoproterenol