Role of substance P on histamine H(3) antagonist-induced scratching behavior in mice.

Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Journal of Pharmacological Sciences (Impact Factor: 2.36). 05/2006; 100(4):297-302.
Source: PubMed


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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    • "The H 3 receptor may modulate the release of histamine directly from DRG neurons or possibly regulate the release of other neurotransmitters such as substance P, which in turn could activate surrounding cells to release histamine. Substance P has found to be involved in the mediation of histamine-induced itch, where H 4 receptor antagonism inhibits substance P-induced pruritus and intradermal injection of a tachykinin NK1 antagonist decreases the pruritus induced by the H 3 receptor antagonist/H 4 receptor agonist clobenpropit (Hossen et al., 2006, Yamaura et al., 2009). A decreased threshold or even an enhanced neurotransmitter release in response to H 3 receptor inverse agonism might activate H 1 receptor and H 4 receptor on a subset of sensory neurons, which in turn could result in the excitation of itch-mediating histamine-sensitive sensory nerves, triggering the itch response (Rossbach et al. 2011). "
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