Nicotinic receptor subtypes mediating relaxation of the normal human clasp and sling fibers of the upper gastric sphincter.
Nicotinic receptor subtypes mediating relaxation of the normal human clasp and sling fibers of the upper gastric sphincter.
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DOI：
10.1111/nmo.12356
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发表时间：
2014-07
影响因子：
3.5
通讯作者：
Miller LS
中科院分区：
文献类型：
--
作者：
Ruggieri MR Sr;Braverman AS;Vegesna AK;Miller LS
胃食管高压区的正常功能对于抗反流屏障的完整性至关重要。机制包括强直收缩以及食管下端括约肌短暂松弛期间张力降低。我们使用器官移植供体组织中现有的亚型选择性烟碱拮抗剂，对介导人上胃括约肌（扣环纤维和吊带纤维）松弛的烟碱受体的药理学进行了表征。有胃食管反流病史或巴雷特食管组织学证据的捐赠者被排除在外。扣环和吊带肌肉纤维条用于三种范例之一。对于范例1，将每个条带暴露于卡巴胆碱，洗涤，暴露于烟碱拮抗剂，然后再次暴露于卡巴胆碱。在范例 2 中，将试纸条暴露于接近最大有效浓度的氨甲酰甲胆碱，然后添加尼古丁。然后清洗条带，暴露于烟碱拮抗剂，然后再次暴露于氨甲酰甲胆碱，随后暴露于尼古丁。在范例3中，将试纸条暴露于氨甲酰甲胆碱，然后暴露于胆碱或金雀花碱。 100 µM 甲基乌头碱对松弛没有抑制作用，消除同聚 α7 亚型。由α4β2亚基组成的亚型也被消除，因为胆碱充当激动剂，而二氢-β-赤霉素无效。由于美加明会阻断松弛，并且胆碱和金雀花氨酸均充当扣环纤维和吊索纤维中的激动剂，因此负责这些松弛的烟碱受体亚型可能由 α3β4β2、α2β4 或 α4β4 亚基组成。
Proper function of the gastroesophageal high pressure zone is essential for the integrity of the antireflux barrier. Mechanisms include tonic contractions as well as the decreased tone during transient lower esophageal sphincter relaxations. We characterized the pharmacology of nicotinic receptors mediating relaxations of the human upper gastric sphincter (clasp and sling fibers) using currently available subtype selective nicotinic antagonists in tissue from organ transplant donors. Donors with either a history of gastroesophageal reflux disease or histologic evidence of Barrett’s esophagus were excluded. Clasp and sling muscle fiber strips were used for one of three paradigms. For paradigm 1, each strip was exposed to carbachol, washed, exposed to nicotinic antagonists then re-exposed to carbachol. In paradigm 2, strips were exposed to a near maximally effective bethanechol concentration then nicotine was added. Strips then were washed, exposed to nicotinic antagonists then re-exposed to bethanechol followed by nicotine. In paradigm 3, strips were exposed to bethanechol then choline or cytisine. 100 µM methyllycaconitine has no inhibitory effects on relaxations, eliminating homomeric α7 subtypes. Subtypes composed of α4β2 subunits are also eliminated because choline acts as an agonist and dihydro-beta-erythroidine is ineffective. Because mecamylamine blocks the relaxations and both choline and cytisine act as agonists in both clasp and sling fibers, the nicotinic receptor subtypes responsible for these relaxations could be composed of α3β4β2, α2β4 or α4β4 subunits.
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DOI：
10.1124/jpet.108.148106
发表时间：
2009-04-01
影响因子：
3.5
作者：
Braverman, Alan S.;Miller, Larry S.;Ruggieri, Michael R., Sr.
通讯作者：
Ruggieri, Michael R., Sr.
影响因子：
8.8
作者：
OPIE, JC;CHAYE, H;STEWARD, DJ
通讯作者：
STEWARD, DJ
DOI：
10.1111/j.1440-1746.2003.03307.x
发表时间：
2004-04-01
影响因子：
4.1
作者：
Tian, ZQ;Liu, JF;Zhang, YF
通讯作者：
Zhang, YF
哺乳动物烟碱乙酰胆碱受体：从结构到功能。
影响因子：
33.6
作者：
Albuquerque EX;Pereira EF;Alkondon M;Rogers SW
通讯作者：
Rogers SW
影响因子：
5.5
作者：
Brasseur, James G.;Ulerich, Rhys;Miller, Larry S.
通讯作者：
Miller, Larry S.