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作者机构:Kinki Univ Sch Pharm Div Pharmacol & Pathophysiol Higashiosaka Osaka 5778502 Japan
出 版 物:《NEUROSCIENCE》 (神经科学)
年 卷 期:2011年第181卷
页 面:257-264页
核心收录:
学科分类:0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学]
主 题:zinc chelator gasotransmitter ion channels allodynia hyperalgesia visceral nociception
摘 要:Luminal hydrogen sulfide (H2S) causes colonic pain and referred hyperalgesia in mice through activation of T-type Ca2+ channels. To test a hypothesis that H2S might chelate and remove endogenous Zn2+ that inhibits the Ca(v)3.2 isoform of T-type Ca2+ channels, facilitating visceral nociception, we asked if intracolonic (***.) administration of Zn2+ chelators mimics H2S-induced visceral nociception. Visceral nociceptive behavior and referred abdominal allodynia/hyperalgesia were determined after ***. administration of NaHS, a donor for H2S, or Zn2+ chelators in mice. Phospholylation of extracellular signal-regulated protein kinase (ERK) in the spinal cord was analyzed by immunohistochemistry. The visceral nociceptive behavior and referred abdominal allodynia/hyperalgesia caused by ***. NaHS in mice were abolished by ***. preadministration of zinc chloride (ZnCl2), known to selectively inhibit Ca(v)3.2, but not Ca(v)3.1 or Ca-v,3.3, isoforms of T-type Ca2+ channels, and by i.p. preadministration of mibefradil, a pan-T-type Ca2+ channel blocker. Two distinct Zn2+ chelators, N,N,N ,N -tetrakis(2-pyridylmethyl)-ehylenediamine (TPEN) and dipicolinic acid, when administered ***., mimicked the NaHS-evoked visceral nociceptive behavior and referred abdominal allodynia/hyperalgesia, which were inhibited by mibefradil and by NNC 55-0396, another T-type Ca2+ channel blocker. Like ***. NaHS, ***. TPEN caused prompt phosphorylation of ERK in the spinal dorsal horn, an effect blocked by mibefradil. Removal of luminal Zn2+ by H2S and other Zn2+ chelators thus produces colonic pain through activation of T-type Ca2+ channels, most probably of the Cav3.2 isoform. Hence, endogenous Zn2+ is considered to play a critical role in modulating visceral pain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.