Histamine H₃ receptors regulate vascular permeability changes in the skin of mast cell-deficient mice

The participation of histamine H₃ receptors in the regulation of skin vascular permeability changes in mast cell-deficient mice was studied. Although intradermal injection of histamine H₃ antagonists, iodophenpropit and clobenpropit, at a dose of 100 nmol/site caused significant increases in skin vascular permeability in both mast cell-deficient (WBB6F1 W/W^v) and wild-type (WBB6F1 +/+) mice, this response was significantly lower in mast cell-deficient mice than in the wild-type controls. Histamine also caused dose-related increases in skin vascular permeability in both wild-type and mast cell-deficient mice. Significant effects were observed at doses of 10 and 100 nmol/site, and no significant difference in skin vascular permeability was observed between mast cell-deficient and wild-type mice. However, histamine contents of dorsal skin in mast cell-deficient mice were significantly lower than in wild-type mice. In addition, the H₁ antagonists diphenhydramine and chlorpheniramine and the NK₁ antagonists, L-732,138 and L-733,060, were able to antagonize H₃ antagonist-induced skin vascular permeability. These results indicated that blockade of H₃ receptors by H₃ antagonists induce skin vascular permeability through mast cell-dependent mechanisms. In addition, histamine and, to a lesser extent substance P are involved in the reaction.