Suppression of passive cutaneous anaphylaxis by pertussis toxin, an islet-activating protein, as a result of inhibition of histamine release from mast cells.
Passive cutaneous anaphylaxis (PCA) produced by antigen challenge to antibody-sensitized rats were interfered with by prior treatment with pertussis toxin, an islet-activating protein (IAP). The degree of interference was dependent on the dose and injection time of IAP; the effect of IAP developed slowly, with a maximal effect being observed 3 days later. Inhibition of PCA by IAP was associated with a decrease in histamine release from peritoneal mast cells, making it very likely that the process affected was mast cell secretion. Much less histamine was discharged in vitro, in response to certain membrane receptor (e.g. IgE receptor) stimulation, from mast cells that had been exposed to IAP than from the cells not exposed. Such an inhibitory effect of IAP was not observed when histamine release was provoked by a calcium ionophore without mediation of membrane receptors. IAP was a stronger inhibitor of histamine release than beta-adrenergic agonists. Further inhibition was produced when a beta-agonist was added to IAP-treated mast cells. The increase in the cellular content of cyclic AMP was associated with beta-agonist-induced, but not with IAP-induced, inhibition of histamine release. Thus, IAP inhibited histamine release by a mechanism in which metabolism of cyclic AMP was not directly involved.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006636:Histamine Release; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001426:Bacterial Proteins; D010566:Virulence Factors, Bordetella; D003189:p-Methoxy-N-methylphenethylamine; D000242:Cyclic AMP; D037342:Pertussis Toxin