Comparative pharmacology of cholecystokinin induced activation of cultured vagal afferent neurons from rats and mice.
Comparative pharmacology of cholecystokinin induced activation of cultured vagal afferent neurons from rats and mice.
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DOI：
10.1371/journal.pone.0034755
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Simasko SM
中科院分区：
文献类型：
--
作者：
Kinch DC;Peters JH;Simasko SM
胆囊收缩素（CCK）通过激活支配上消化道的迷走神经传入神经元促进饱足过程。最近的研究表明CCK通过钌红（RuR）敏感通路作用于这些神经元，该通路涉及瞬时受体电位（TRP）通道的香草酸（V）亚家族成员。为了进一步测试这一机制，小鼠提供了一个理想的模型，其中可以应用遗传工具。然而，CCK在小鼠中是否通过类似的机制起作用尚未确定。在本研究中，我们探讨了CCK的行动，从SD大鼠和两个品系的小鼠，C57 BL/6和BalbC的结状神经元分离，使用基于荧光的钙成像。除少数例外，从所有物种/菌株中分离出的结状神经元表现相似。它们都对短暂的去极化有反应，并伴有大量钙瞬变。一个显着的子集的神经元响应辣椒素（CAP），TRPV1激动剂，虽然从C57 BL/6的神经元CAP比SD大鼠或BalbC小鼠敏感10倍，和一个显着较小的分数BalbC小鼠的神经元响应CAP。CCK-8剂量依赖性地激活了一个亚群的神经元，具有相似的剂量依赖性，反应百分比，CCK和CAP反应之间的重叠。在所有物种/菌株CCK-8诱导的激活显着衰减（但不完全阻断）预处理与TRPV通道阻断剂RuR。令人惊讶的是，CCK类似物JMV-180，据报道在大鼠中具有纯拮抗性质，但在小鼠中具有混合激动剂/拮抗剂性质，在大鼠和小鼠神经元中表现为CCK的纯拮抗剂。JMV-180在该体外制剂中的纯拮抗作用表明，先前报道的JMV-180对大鼠与小鼠饱食的差异作用必须由迷走神经传入激活以外的部位介导。
Cholecystokinin (CCK) facilitates the process of satiation via activation of vagal afferent neurons innervating the upper gastrointestinal tract. Recent findings indicate CCK acts on these neurons via a ruthenium red (RuR) sensitive pathway that involves members of the vanilloid (V) subfamily of transient receptor potential (TRP) channels. To further test this mechanism, the mouse provides an ideal model in which genetic tools could be applied. However, whether CCK acts by similar mechanism(s) in mice has not been determined. In the present study we explored the actions of CCK on nodose neurons isolated from Sprague Dawley (SD) rat and two strains of mice; C57BL/6 and BalbC using fluorescence-based calcium imaging. With minor exceptions nodose neurons isolated from all species/strains behaved similarly. They all respond to brief depolarization with a large calcium transient. A significant subset of neurons responded to capsaicin (CAP), a TRPV1 agonist, although neurons from C57BL/6 were 10-fold more sensitive to CAP than SD rats or BalbC mice, and a significantly smaller fraction of neurons from BalbC mice responded to CAP. CCK-8 dose-dependently activated a subpopulation of neurons with similar dose dependency, percent responders, and overlap between CCK and CAP responsiveness. In all species/strains CCK-8 induced activation was significantly attenuated (but not completely blocked) by pretreatment with the TRPV channel blocker RuR. Surprisingly, the CCK analogue JMV-180, which is reported to have pure antagonistic properties in rat but mixed agonist/antagonist properties in mice, behaved as a pure antagonist to CCK in both rat and mouse neurons. The pure antagonistic action of JMV-180 in this in vitro preparation suggests that prior reported differential effects of JMV-180 on satiation in rats versus mouse must be mediated by a site other than vagal afferent activation.
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影响因子：
--
作者：
MATOZAKI, T;MARTINEZ, J;WILLIAMS, JA
通讯作者：
WILLIAMS, JA
影响因子：
4.8
作者：
Peters, JH;Karpiel, AB;Simasko, SM
通讯作者：
Simasko, SM
影响因子：
16.2
作者：
Peters, James H.;McDougall, Stuart J.;Fawley, Jessica A.;Smith, Stephen M.;Andresen, Michael C.
通讯作者：
Andresen, Michael C.
影响因子：
2.5
作者：
Correll, CC;Phelps, PT;Greenfeder, S
通讯作者：
Greenfeder, S
DOI：
10.1152/ajpgi.00249.2002
发表时间：
2002-12-01
影响因子：
4.5
作者：
Powley, TL;Phillips, RJ
通讯作者：
Phillips, RJ