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Histamine H1- and H2-receptor involvement in eosinophil infiltration and the microvascular changes associated with cutanneous anaphylaxis
Authors:Dr D F Woodward  C S Spada  S B Hawley  A L Nieves
Institution:(1) Dept. of Pharmacology, Allergan Pharmaceuticals, 2525 Dupont Drive, 92715 Irvine, CA, U.S.A.
Abstract:Several substances alter eosinophil motility, but the relative importance of these putative mediators in immediate hypersensitivity remains unclear. The present study has reinvestigated the role of histamine in type I allergic eosinophil infiltration, and the temporally associated microvascular events, by examining the effect of H1-and H2-receptor antagonist pretreatment. A combination of cimetidine and pyrilamine significantly reduced eosinophil accumulation, whereas neither antagonist alone was effective. Similarly, cutaneous hyperemia, measured indirectly as ear surface temperature, was reduced only by the cimetidine-pyrilamine combination. Pyrilamine partially attenuated the increase in microvascular permeability, but the addition of cimetidine provided no further reduction.It appears that histamine participates significantly in mediating both the microvascular changes and the eosinophil infiltration evoked by cutaneous anaphylaxis. The histaminergic component of increased microvascular permeability appears to be an H1-receptor mediated phenomenon. However, blockade of both H1-and H2-receptor subtypes is required to inhibit the hyperemia and eosinophil infiltration responses.
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