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《Acta Pharmaceutica Sinica》 2005-01
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5-HT_2 receptor mediated the potentiation of GABA-activated current in the membrane of the dorsal root ganglion neurons of rat

AN Jie 1, CHEN Chang-hua 3, GUAN Bing-cai 1, TANG Ming 2, YU Cheng-gao 2, LI Zhi-wang 1* (1. Department of Neurobiology, 2. Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China; 3. Shandong Armed Police Force Hospital, Jinan 250014, China)  
Aim To explore the modulation of 5-HT on GABA-activated current (I GABA) in the membrane of rat dorsal root ganglion (DRG) neurons and its mechanism. Methods Rat DRG neurons were isolated mechanically and enzymatically, on which whole-cell patch clamp recording and repatch technique for intracellular dialysis were performed. Results In the majority of neurons examined (92.0%, 69/75) GABA induced a concentration-dependent inward current. In neurons sensitive to GABA preapplication of 5-HT produced potentiation effect (82.6%, 57/69) on I GABA. Preapplication of 5-HT at concentrations of 1×10 -6, 1×10 -5, 1×10 -4 and 1×10 -3 mol·L -1 potentiated I GABA by ( 35±8)% (n=8), (47±11)% (n=10), (65±17)% (n=9) and (75±18)% (n=11), respectively. This effect was mimicked by α-methyl-5-HT (1×10 -6 mol·L -1), a specific 5-HT 2 receptor agonist, and reversed by cyproheptadine, a selective 5-HT 2 receptor antagonist. The potentiation of I GABA by 5-HT was irrespective to whether the I 5-HT presents or not in a subset of neurons. The concentration-response curves for GABA before and after pretreatment with 5-HT manifested the same threshold value and similar EC 50 (2.0×10 -5 and 1.9×10 -5 mol·L -1, respectively), while the maximal value of I GABA for the latter was 33.6% higher than that for the former. Intracellular dialysis with GDP-β-S or H-7 abolished the potentiation of I GABA by 5-HT, while H-9 did not. Conclusion 5-HT can potentiate GABA-activated current via PKC-dependent phosphorylation of GABA A receptor following the activation of 5-HT 2 receptor.
【Fund】: NationalNaturalScienceFoundationofChina(39870259).
【CateGory Index】: Q421
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