The purpose of the present study was to investigate the involvement of chemical mediators, other than histamine, in the scratching behavior induced by H
3 antagonists. Scratching behavior was induced by the histamine H
3 antagonists iodophenpropit and clobenpropit (10 nmol/site) when they were injected intradermally into the rostral part of the back of mast-cell-deficient (WBB6F1 W/W
v) and wild-type (WBB6F1 +/+) mice. Subsequently, the effect of spantide, a tachykinin NK
1 antagonist, was measured for 60 min. The effects of the H
3 antagonists on in vitro histamine release from rat peritoneal mast cells were also investigated. When spantide was injected intradermally at a dose of 0.5 nmol/site, it significantly inhibited the response. Furthermore, iodophenpropit and clobenpropit (10
−6 – 10
−8 M) did not induce histamine release in isolated rat peritoneal mast cells. Our results indicate that substance P is involved in the skin responses elicited by the histamine H
3 antagonists. Moreover, the fact that these histamine H
3 antagonists did not induce significant increases in the histamine release from rat peritoneal mast cells suggests that the histamine H
3 receptor may not be present in the peripheral cells considered in this study.
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