An analysis of the specificity in pharmacological inhibition of the passive cutaneous anaphylaxis reaction in mice and rats.
An antiserum obtained from mice, immunized to produce an antiovalbumin antibody of the IgE type, was employed in a 48-hour passive cutaneous anaphylaxis (PCA) reaction in both mice and rats. The antiserum contained an antibody which, "fixed" to skin for at least 6 days, was heat labile and eluted from diethylaminoethyl cellulose in the reagin peak. In both rats and mice, the PCA reaction was mediated by a combination of histamine and serotonin and was inhibited by specific antagonists. Various drugs were tested for inhibition of the PCA reaction in recipients also injected with compound 48/80 and histamine. Drugs which have been reported to cause an increase in intracellular cyclic adenosine monophosphate levels [prostaglandins (PG) E1 and E2 and theophylline] all selectively inhibited the PCA reaction at low doses. By varying the length of time of drug administration prior to antigen challenge, the pharmacological half-life of PGE1 was determined to be approximately 9 minutes. At high doses, theophylline also inhibited the 48/80 reaction, and PGE1 inhibited all three reactions, whereas PGE2 only inhibited PCA. Disodium cromoglycate, when given to rats, inhibited only the PCA reaction without effect on the 48/80 or histamine wheal. It was totally ineffective on any parameter measured in the mouse. It is suggested that the PCA reaction in the rodent is induced by an IgE-like antibody and mediator release is, to some extent, sensitive to intracellular levels of cyclic adenosine monophosphate. Analysis of the specificity of drug activity depends upon dose-response studies, species differences and consideration of nonspecific systemic effects.
D000818:Animals; D000917:Antibody Formation; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E; D007249:Inflammation / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis; D051381:Rats; D012867:Skin / Q000276:immunology; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D010047:Ovalbumin