Electroacupuncture modulates v1PAG release of GABA through presynaptic cannabinoid CB1 receptors
Electroacupuncture modulates v1PAG release of GABA through presynaptic cannabinoid CB1 receptors
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DOI：
10.1152/japplphysiol.91648.2008
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发表时间：
2009-06-01
影响因子：
3.3
通讯作者：
Longhurst, John C.
中科院分区：
文献类型：
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作者：
Fu, Liang-Wu;Longhurst, John C.
Fu L-W，Longhurst JC.电针通过突触前大麻素CB 1受体调节GABA的v1 PAG释放。J Appl Physiol 106：1800-1809，2009.首次发表于2009年4月9日; doi：10.1152/japplphysiol.91648.2008。以往的研究表明，电针通过激活下丘脑弓状核（ARC）、中脑导水管周围灰质（v1 PAG）和延髓头端腹外侧区（rVLM）的长环通路来减弱交感神经兴奋性反射反应。ARC中的神经元向v1 PAG提供兴奋性输入，而v1 PAG抑制rVLM中的神经元活动。γ-氨基丁酸（GABA）和谷氨酸（Glu）已在v1 PAG中鉴定。内源性大麻素（Endocannabinoids，ECs）作为非典型神经递质，通过突触前大麻素1型（CB 1）受体机制抑制下丘脑和中脑中两种神经递质的释放。EC系统在背侧被观察到，但在v1 PAG中没有。由于目前还不确定是否EC的影响GABA和Glu在v1 PAG，本研究测试的假设，EA调制这些神经递质的释放在v1 PAG通过突触前CB 1受体机制。我们测量释放的GABA和Glu的同时，通过使用HPLC来评估收集的样品与微透析探针插入单侧到完整的麻醉大鼠的v1 PAG。电针P5-6穴28 min（2 Hz，2-4 mA，0.5 ms），可使GABA释放量减少39%，15 min后减少44%。电针后35分钟，GABA浓度恢复到电针前水平。与此相反，假电针并没有改变v1 PAG GABA浓度。用选择性CB 1受体拮抗剂AM 251阻断CB 1受体，可逆转EA调制的GABA浓度变化，而向v1 PAG中微量注射载体并不改变EA调制的GABA变化。此外，我们在EA期间未观察到v1 PAG Glu浓度的变化，尽管Glu的基线浓度远高于GABA（3，541 +/- 373 vs. 33.8 +/- 8.7 nM，Glu vs. GABA）。这些结果表明，EA调制交感神经兴奋性反射反应，减少释放GABA，但不Glu，在v1 PAG，最有可能通过突触前CB 1受体机制。
Fu L-W, Longhurst JC. Electroacupuncture modulates v1PAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 106: 1800-1809, 2009. First published April 9, 2009; doi:10.1152/japplphysiol.91648.2008.-Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (v1PAG), and rostral ventrolateral medulla (rVLM). Neurons in the ARC provide excitatory input to the v1PAG, whereas the v1PAG inhibits neuronal activity in the rVLM. gamma-Aminobutyric acid (GABA) and glutamate (Glu) have been identified in the v1PAG. Endocannabinoids (ECs), acting as atypical neurotransmitters, inhibit the release of both neurotransmitters in the hypothalamus and midbrain through a presynaptic cannabinoid type 1 (CB1) receptor mechanism. The EC system has been observed in the dorsal but not in the v1PAG. Since it is uncertain whether ECs influence GABA and Glu in the v1PAG, the present study tested the hypothesis that EA modulates the release of these neurotransmitters in the v1PAG through a presynaptic CB1 receptor mechanism. We measured the release of GABA and Glu simultaneously by using HPLC to assess samples collected with microdialysis probes inserted unilaterally into the v1PAG of intact anesthetized rats. Twenty-eight min of EA (2 Hz, 2-4 mA, 0.5 ms) at the P5-6 acupoints reduced the release of GABA by 39% during EA and by 44% 15 min after EA. Thirty-five minutes after EA, GABA concentrations returned to pre-EAlevels. In contrast, sham EA did not change the v1PAG GABA concentration. Blockade of CB1 receptors with AM251, a selective CB1 receptor antagonist, reversed the EA-modulated changes in GABA concentration, whereas micro-injection of vehicle into the v1PAG did not alter EA-modulated GABA changes. In addition, we observed no changes in the v1PAG Glu concentrations during EA, although the baseline concentration of Glu was much higher than that of GABA (3,541 +/- 373 vs. 33.8 +/- 8.7 nM, Glu vs. GABA). These results suggest that EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA, but not Glu, in the v1PAG, most likely through a presynaptic CB1 receptor mechanism.