Role of Substance P on Histamine H3 Antagonist-Induced Scratching Behavior in Mice

Abstract

Abstract. 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 mastcell-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.

Substance P is involved in the effect of histamine H3 receptor agonist, Sch 50971 on nasal allergic symptoms in mice

“…It was also found in the present study that clobenpropitinduced nasal symptoms were antagonized by pretreatment with tachykinin NK 1 receptor antagonist, L-733,060. Similar findings were also reported by Hossen et al [17] who found that a tachykinin NK 1 receptor antagonist, spantide, inhibited clobenpropit and iodophenpropit-induced scratching behavior in mice. It has been considered that H 3 receptors modulate substance P release [5,19]; therefore, blocking H 3 receptors results in substance P release.…”

“…In addition, there are some findings that H 1 receptor antagonists caused no inhibition on the nasal signs induced by capsaicin and substance P, though the nasal signs induced by histamine were antagonized by H 1 receptor antagonists [22,23]. We have reported that the scratching behavior induced by H 3 receptor antagonists was mediated by substance P, but not histamine [17]. In addition, Matsubara et al [25] demonstrated that (R)-α-methylhistamine inhibited plasma protein extravasation within the dura mater induced by capsaicin in rats and guinea pigs, and the extravasation caused by substance P was not blocked by (R)-α-methylhistamine.…”

“…Indeed, McLeod et al demonstrated that Sch 50971 suppressed neurogenic inflammation by inhibition of the release of neuropeptides via H 3 receptors in the neurogenic migraine model of guinea pig [14]. Moreover, we previously reported that H 3 receptor antagonists such as clobenpropit and iodophenpropit induced scratching behavior in mice through substance P but not histamine [15][16][17]. These findings led us to presume that H 3 receptors regulate allergic rhinitis via peripheral sensory nerves including substance P.…”

Central histamine H3receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS

“…The diabetes-associated allele of Idd4.1 was identified as a hypofunctional mutant of Tprv1 that influences peripheral neuronal control of ␤ cell stress and islet inflammation in NOD mice via a proinflammatory state (67). Importantly, H 3 R stimulation has been shown to prevent capsaicin-induced substance P release from C-fibers (68,69). By analogy, in our model H 3 R (Eae8) presynaptic signaling in the CNS or in the peripheral nervous system could affect T cell gene expression.…”

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on scratching behavior in mice

“…In these diseases, scratching provoked by itching aggravates skin lesions and worsens dermatitis [2]. It has been assumed that the important mediators for causing itching are histamine, prostaglandins, tryptase, IL-2 and substance P [3][4][5][6][7]. On the other hand, it has become clear that nerve growth factor (NGF) stimulates the extension and function of sensory nerve C fibers.…”