The purpose of the present study was to investigate the involvement of chemical mediators, other than histamine, in the scratching behavior induced by H3 antagonists. Scratching behavior was induced by the histamine H3 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/Wv) and wild-type (WBB6F1 +/+) mice. Subsequently, the effect of spantide, a tachykinin NK1 antagonist, was measured for 60 min. The effects of the H3 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 H3 antagonists. Moreover, the fact that these histamine H3 antagonists did not induce significant increases in the histamine release from rat peritoneal mast cells suggests that the histamine H3 receptor may not be present in the peripheral cells considered in this study.
The Japanese Pharmacological Society 2006