title: TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch.
abstract: Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)-a histamine H4 receptor special agonist under cutaneous injection-obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3-50 μM) could also induce a dose-dependent increase in intracellular Ca(2+) ([Ca(2+)]i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca(2+) responses. In addition, immepip-induced [Ca(2+)]i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons' responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Tunyu
authors.initials: T
authors.lastname: Jian
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Niuniu
authors.initials: N
authors.lastname: Yang
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Zhu
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yu
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Changming
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Shi
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: He
authors.affiliation: College of Life Science, Nanjing Normal University, Nanjing 210046, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lan
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China; College of Basic Medicine, Guangxi University of Chinese Medicine, 13 Wuhe Road, Nanning 530200, China.
authors.forename: Guanyi
authors.initials: G
authors.lastname: Wu
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
authors.forename: Zongxiang
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011537:Pruritus / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000083:Acetanilides; D000178:Acrylamides; D000982:Antipruritics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017442:Histamine Agonists; C498829:Hrh4 protein, mouse; D007093:Imidazoles; D010880:Piperidines; D011687:Purines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D010738:Type C Phospholipases; D002211:Capsaicin; D002118:Calcium
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