title: An analysis of the specificity in pharmacological inhibition of the passive cutaneous anaphylaxis reaction in mice and rats.
abstract: 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.
mesh_terms: 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
chemical_list: D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D010047:Ovalbumin