Pharmacological investigations of the cellular transduction pathways used by cholecystokinin to activate nodose neurons.
Pharmacological investigations of the cellular transduction pathways used by cholecystokinin to activate nodose neurons.
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DOI：
10.1016/j.autneu.2011.05.004
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发表时间：
2011-10-28
影响因子：
2.7
通讯作者：
Simasko, Steven M.
中科院分区：
文献类型：
--
作者：
Zhao, Huan;Kinch, Dallas C.;Simasko, Steven M.
胆囊收缩素（CCK）直接激活迷走神经传入神经元，导致协调胃肠功能和饱食。在体外，CCK对分离的迷走神经传入神经元的作用是通过激活香草酸家族的瞬时受体电位（TRPV）阳离子通道介导的，导致膜去极化和胞浆钙增加。然而，CCK受体和通道开放之间的这一过程中涉及的细胞转导途径尚未确定。为了解决这个问题，我们监测CCK诱导的细胞内钙反应在解离结状神经元从大鼠在存在或不存在的试剂，与各种细胞内信号通路相互作用。我们发现，磷脂酶C（PLC）抑制剂U-73122显着衰减CCK诱导的反应，而无活性的类似物U-73433没有影响。对CCK的反应也通过用PLC刺激剂m-3 M3 FBS短暂预处理而交叉脱敏。总之，这些观察结果强烈支持PLC参与CCK对迷走神经传入神经元的影响。相反，磷脂酶A2，蛋白激酶A和磷脂酰肌醇3-激酶的药理学拮抗作用表明，它们在CCK诱导的结状神经元钙反应中并不重要。对PLC下游细胞通路的进一步研究表明，无论是蛋白激酶C（PKC）还是甘油二酯（DAG）的生成或细胞内钙库的钙释放都不参与对CCK的反应。这些结果表明，改变膜磷脂酰肌醇4，5-二磷酸（PIP 2）含量PLC活动介导CCK诱导的钙反应，这一途径可能是基础的迷走神经介导的行动CCK诱导饱食和改变胃肠道功能。
Cholecystokinin (CCK) directly activates vagal afferent neurons resulting in coordinated gastrointestinal functions and satiation. In vitro, the effects of CCK on dissociated vagal afferent neurons are mediated via activation of the vanilloid family of transient receptor potential (TRPV) cation channels leading to membrane depolarization and an increase in cytosolic calcium. However, the cellular transduction pathway(s) involved in this process between CCK receptors and channel opening have not been identified. To address this question, we monitored CCK-induced cytosolic calcium responses in dissociated nodose neurons from rat in the presence or absence of reagents that interact with various intracellular signaling pathways. We found that the phospholipase C (PLC) inhibitor U-73122 significantly attenuated CCK-induced responses, whereas the inactive analog U-73433 had no effect. Responses to CCK were also cross-desensitized by a brief pretreatment with m-3M3FBS, a PLC stimulator. Together these observations strongly support the participation of PLC in the effects of CCK on vagal afferent neurons. In contrast, pharmacological antagonism of phospholipase A2, protein kinase A, and phosphatidylinositol 3-kinase revealed that they are not critical in the CCK-induced calcium response in nodose neurons. Further investigations of the cellular pathways downstream of PLC showed that neither protein kinase C (PKC) nor generation of diacylglycerol (DAG) or release of calcium from intracellular stores participates in the response to CCK. These results suggest that alteration of membrane phosphatidylinositol 4,5-bisphosphate (PIP2) content by PLC activity mediates CCK-induced calcium response and that this pathway may underlie the vagally-mediated actions of CCK to induce satiation and alter gastrointestinal functions.
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CCK-8S 对 GABA 诱导的大鼠背根神经节去极化的调节作用
影响因子：
2.9
作者：
Ma, Ke-Tao;Si, Jun-Qiang;Zhu, Li
通讯作者：
Zhu, Li
DOI：
10.1037/h0034870
发表时间：
1973-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
GIBBS, J;YOUNG, RC;SMITH, GP
通讯作者：
SMITH, GP
影响因子：
5.5
作者：
Peters, JH;Ritter, RC;Simasko, SM
通讯作者：
Simasko, SM
影响因子：
4.7
作者：
Morioka, N;Takeda, K;Nakata, Y
通讯作者：
Nakata, Y
影响因子：
4.8
作者：
Hu, HZ;Gu, QH;Zhu, MX
通讯作者：
Zhu, MX