Role of substance P on histamine H(3) antagonist-induced scratching behavior in mice.
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 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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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 · 9.81 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; 4:29. DOI:10.1186/1744-8069-4-29 · 3.53 Impact Factor
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ABSTRACT: Existing data on the expression of H(4) histamine receptor in the CNS are conflicting and inconclusive. In this report, we present the results of experiments that were conducted in order to elucidate H(4) receptor expression and localization in the brain, spinal cord, and dorsal root ganglia (DRG). Here we show that transcripts of H(4) receptor are present in all analyzed regions of the human CNS, including spinal cord, hippocampus, cortex, thalamus and amygdala, with the highest levels of H(4) mRNA detected in the spinal cord. In rat, H(4) mRNA was detected in cortex, cerebellum, brainstem, amygdala, thalamus and striatum. Very low levels of H(4) mRNA were detected in hypothalamus, and no H(4) signal was detected in the rat hippocampus. Fairly low levels of H(4) mRNA were detected in examined peripheral tissues including spleen and liver. Interestingly, strong expression of H(4) mRNA was detected in the rat DRG and spinal cord. Immunohistochemical analysis revealed expression of H(4) receptors on neurons in the rat lumbar DRG and in the lumbar spinal cord. Our observations provide evidence of the H(4) presence in both human and rodent CNS and offer some insight into possible role of H(4) in itch and pain.Brain research 12/2008; 1250:41-8. DOI:10.1016/j.brainres.2008.11.018 · 2.83 Impact Factor