Modulatory effect of CCK-8S on GABA-induced depolarization from rat dorsal root ganglion
Modulatory effect of CCK-8S on GABA-induced depolarization from rat dorsal root ganglion
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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
DOI：
10.1016/j.brainres.2006.08.094
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发表时间：
2006-11-22
期刊：
影响因子：
2.9
通讯作者：
Zhu, Li
中科院分区：
文献类型：
--
作者：
Ma, Ke-Tao;Si, Jun-Qiang;Zhu, Li
CCK是一种脑肠肽，在哺乳动物的胃肠道和脑中均有丰富的分布。胆囊收缩素的硫酸化八肽片段（CCK-8 S）已被证明参与许多生理功能，如行为、焦虑、学习/记忆过程和神经病理性疼痛。CCK-8 S是最强的内源性抗阿片物质之一，并抑制阿片肽介导的γ-氨基丁酸（GABA）释放的“突触前抑制”。本研究利用细胞内记录技术证实CCK-8 S对GABA诱发的大鼠背根神经节（DRG）神经元膜去极化有调节作用。浴用CCK-8 S可引起大部分大鼠DRG神经元的膜去极化。除极被普鲁胺阻断，但不被LY 225910阻断。CCK-8 S预处理可浓度依赖性地抑制GABA诱发的去极化。CCK-8 S的抑制作用也呈时间依赖性，在2 min左右达到峰值。CCK-8 S的抑制作用可被CCK-B受体拮抗剂LY 225910、磷脂酶C抑制剂U 73122、蛋白激酶C抑制剂白屈菜红碱和钙离子螯合剂BAPTA-AM所抑制。蛋白激酶A抑制剂H-89不影响CCK-8 S的作用。结果提示CCK-8 S通过激活CCK-B受体，进而激活胞内PLC-Ca ~（2+）-PKC级联反应，抑制GABA-A受体功能。因此，CCK-8 S可能通过抑制GABA引起的“突触前抑制”而增强伤害性信息的传递，这可能解释了CCK-8 S在初级感觉信息（尤其是疼痛）调制中的作用。(c)2006 Elsevier B. V.保留所有权利。
CCK is a brain-gut peptide that is abundantly distributed in both gastrointestinal tract and mammalian brain. The sulfated octapeptide fragment of cholecystokinin (CCK-8S) has been shown to be involved in numerous physiological functions such as behavior, anxiety, learning/memory processes and neuropathic pain. CCK-8S is one of the strongest endogenous anti-opioid substances and suppresses opioid peptides-mediated 'pre-synaptic inhibition' of gamma-aminobutyric acid (GABA) release. Here we provide evidence that CCK-8S modulates GABA-evoked membrane depolarization in rat dorsal root ganglion (DRG) neurons using intracellular recording technique. Bath application CCK-8S-induced membrane depolarization in most of the rat DRG neurons. The depolarization was blocked by prolumide but not LY225910. Pretreatment with CCK-8S suppressed the GABA-evoked depolarization in a concentration-dependent manner. The CCK-8S inhibition was also time-dependent and reached the peak at about 2 min. The inhibitory effect of CCK-8S was strongly suppressed by pre-incubation of CCK-B receptor antagonist LY225910, phospholipase C inhibitor U73122, protein kinase C inhibitor chelerythrine and calcium chelator BAPTA-AM, respectively. The protein kinase A inhibitor H-89 did not affect CCK-8S effect. The results suggest that CCK-8S inhibits GABA-A receptor function by activation of CCK-B receptor followed by activation of intracellular PLC-Ca2+-PKC cascade. Thus, CCK-8S might enhance nociceptive information transmission through inhibition of the "presynaptic inhibition" evoked by GABA, which may explain its role in modulation of primary sensory information (especially pain). (c) 2006 Elsevier B.V. All rights reserved.