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.
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.
- "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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ABSTRACT: Histamine (HA), a biogenic amine with a broad spectrum of activities in both physiological and pathological settings, plays a key regulatory role in experimental allergic encephalomyelitis, the autoimmune model of multiple sclerosis. HA exerts its effect through four G protein-coupled receptors designated HA receptor H1, H2, H3, and H4. We report here that, compared with wild-type animals, mice with a disrupted HA H3 receptor (H3RKO), the expression of which is normally confined to cells of the nervous system, develop more severe disease and neuroinflammation. We show that this effect is associated with dysregulation of blood-brain barrier permeability and increased expression of MIP-2, IP-10, and CXCR3 by peripheral T cells. Our data suggest that pharmacological targeting of the H3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease.Proceedings of the National Academy of Sciences 07/2007; 104(24):10146-51. DOI:10.1073/pnas.0702291104 · 9.67 Impact Factor
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ABSTRACT: Itch is one of the major complications of skin diseases. Although there are various substances that induce itch or pruritus, it is evident that histamine is the best known endogenous agent that evokes itch. Even though histamine-induced itch has been studied for some time, the underlying mechanism of itch is just beginning to emerge. Although various downstream signaling pathways of histamine receptors have been revealed, more studies are required to determine the cause of histamine-induced itch. It appears that itch and pain involve different neuronal pathways. Pain generally inhibits itch, which indicates an inter-communication between the two. Complex interactions between itch and pain may be expected based on reports on disease states and opioids. In this review, we discuss the molecular mechanism and the pharmacological aspects of histamine-induced itch. Especially, the underlying mechanism of TRPV1 (an anti-pruritus target) has been determined to some extent.Molecular Pain 02/2008; 4(1):29. DOI:10.1186/1744-8069-4-29 · 3.65 Impact Factor
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