Bell J K, McQueen D S, Rees J L
Division of Neuroscience, College of Medicine, University of Edinburgh, Edinburgh EH8 9JZ, Scotland, UK.
Br J Pharmacol. 2004 May;142(2):374-80. doi: 10.1038/sj.bjp.0705754. Epub 2004 Apr 5.
The role of histamine H(1), H(2), H(3) and H(4) receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and "itch" assessed by quantifying the scratching evoked. Histamine (0.03-80 micromol), histamine-trifluoromethyl-toluidine (HTMT, H(1) agonist, 0.002-2 micromol), clobenpropit (H(4) agonist, H(3) antagonist, 0.002-0.6 micromol) and to a lesser extent imetit (H(3)/H(4) agonist, 0.03-3 micromol) all induced dose-dependent scratching. Dimaprit (H(2) agonist, 0.04-40 micromol) did not cause scratching. Mepyramine (H(1) antagonist, 20 mg kg(-1), i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H(3) or H(4) agonists. Thioperamide (H(3)/H(4) antagonist, 20 mg kg(-1), i.p.) reduced scratching induced by histamine, H(3) and H(4) agonists, but not that caused by HTMT. The non-sedating H(1) antagonist, terfenadine, also significantly reduced the scratching induced by the H(1) agonist, HTMT. Cimetidine (H(2) antagonist, 20 mg kg(-1), i.p.) did not affect histamine-induced scratching. These results indicate that activation of histamine H(4) receptors causes itch in mice, in addition to the previously recognised role for H(1) receptors in evoking itch. Histamine H(4) receptor antagonists therefore merit investigation as antipruritic agents.
在雌性BalbC小鼠中研究了组胺H(1)、H(2)、H(3)和H(4)受体在组胺诱导的急性瘙痒中的作用。通过将致痒原皮内注射到颈部背部来诱发抓挠，并通过量化诱发的抓挠来评估“瘙痒”。组胺（0.03 - 80微摩尔）、组胺-三氟甲基甲苯胺（HTMT，H(1)激动剂，0.002 - 2微摩尔）、氯苯丙哌嗪（H(4)激动剂，H(3)拮抗剂，0.002 - 0.6微摩尔）以及程度较轻的碘替丁（H(3)/H(4)激动剂，0.03 - 3微摩尔）均诱导剂量依赖性抓挠。二甲双胍（H(2)激动剂，0.04 - 40微摩尔）未引起抓挠。美吡拉敏（H(1)拮抗剂，20毫克/千克，腹腔注射）减少了组胺和HTMT诱发的抓挠，但不影响H(3)或H(4)激动剂引起的抓挠。硫代哌啶（H(3)/H(4)拮抗剂，20毫克/千克，腹腔注射）减少了组胺、H(3)和H(4)激动剂诱导的抓挠，但不影响HTMT引起的抓挠。非镇静性H(1)拮抗剂特非那定也显著减少了H(1)激动剂HTMT诱导的抓挠。西咪替丁（H(2)拮抗剂，20毫克/千克，腹腔注射）不影响组胺诱导的抓挠。这些结果表明，除了先前认识到的H(1)受体在诱发瘙痒中的作用外，组胺H(4)受体的激活也会导致小鼠瘙痒。因此，组胺H(4)受体拮抗剂作为止痒剂值得研究。
