Rapid Glucocorticoid-Induced Activation of TRP and CB1 Receptors Causes Biphasic Modulation of Glutamate Release in Gastric-Related Hypothalamic Preautonomic Neurons.
Rapid Glucocorticoid-Induced Activation of TRP and CB1 Receptors Causes Biphasic Modulation of Glutamate Release in Gastric-Related Hypothalamic Preautonomic Neurons.
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DOI：
10.3389/fnins.2013.00003
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发表时间：
2013
影响因子：
4.3
通讯作者：
Smith BN
中科院分区：
文献类型：
--
作者：
Boychuk CR;Zsombok A;Tasker JG;Smith BN
糖皮质激素通过诱导内源性信使的逆行释放，快速调节下丘脑室旁核(PVN)神经内分泌细胞的突触输入。在这里，我们用全细胞膜片钳记录的方法研究了地塞米松(DEX)对兴奋性突触传入与摄食相关的自主前神经PVN神经元的快速影响。在∼中，50%的胃相关植物前核神经元出现双相突触反应，其特征是微小兴奋性突触后电流(MEPSC)频率在9 内迅速而短暂地升高，随后mEPSC频率降低，其余细胞仅表现为mEPSC频率降低。大麻素受体激动剂阿南达胺(AEA)和Win 55,212-2可模拟mEPSC频率的晚期下降，CB1受体拮抗剂AM251可阻断这种下降。AEA模拟双相地塞米松效应。用辣椒素激活瞬时受体电位香草型1型受体和用4-α-PDD激活TRPV4受体可模拟早期mEPSCs的增加。在TRPV1基因敲除小鼠中，这种增加被选择性的TRPV1拮抗剂减少，但不被阻止；广谱的TRPV拮抗剂钌红以及选择性TRPV1和TRPV4拮抗剂的联合应用完全阻断了这种增加。地塞米松的作用可通过细胞内注射G蛋白抑制剂GDPPVN S来完全阻止。因此，地塞米松通过双向调节突触谷氨酸进入胃相关的下丘脑室旁核神经元亚群，这可能是通过诱导逆行信使来实现的。这种作用包括TRPV1/4受体介导的一过性增加和随后CB1受体介导的谷氨酸释放抑制。谷氨酸对下丘脑室旁核神经元的多相调节代表了糖皮质激素和内源性大麻素控制自主神经输出的一种以前未被意识到的复杂性。
Glucocorticoids rapidly regulate synaptic input to neuroendocrine cells in the hypothalamic paraventricular nucleus (PVN) by inducing the retrograde release of endogenous messengers. Here we investigated the rapid effects of dexamethasone (DEX) on excitatory synaptic input to feeding-related, preautonomic PVN neurons using whole-cell patch-clamp recordings. In ∼50% of identified gastric-related preautonomic PVN neurons, DEX elicited a biphasic synaptic response characterized by an initial rapid and transient increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), followed by a decrease in mEPSC frequency within 9 min; remaining cells displayed only a decrease in mEPSC frequency. The late-phase decrease in mEPSC frequency was mimicked by the cannabinoid receptor agonists anandamide (AEA) and WIN 55,212-2, and it was blocked by the CB1 receptor antagonist AM251. The biphasic DEX effect was mimicked by AEA. The early increase in mEPSCs was mimicked by activation of transient receptor potential vanilloid type 1 (TRPV1) receptors with capsaicin and by activation of TRPV4 receptors with 4-α-PDD. The increase was reduced, but not blocked, by selective TRPV1 antagonists and in TRPV1 knockout mice; it was blocked completely by the broad-spectrum TRPV antagonist ruthenium red and by combined application of selective TRPV1 and TRPV4 antagonists. The DEX effects were prevented entirely by intracellular infusion of the G-protein inhibitor, GDPβS. Thus, DEX biphasically modulates synaptic glutamate onto a subset of gastric-related PVN neurons, which is likely mediated by induction of a retrograde messenger. The effect includes a TRPV1/4 receptor-mediated transient increase and subsequent CB1 receptor-mediated suppression of glutamate release. Multiphasic modulation of glutamate input to PVN neurons represents a previously unappreciated complexity of control of autonomic output by glucocorticoids and endogenous cannabinoids.
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影响因子：
3.3
作者：
Cristino, L.;De Petrocellis, L.;Di Marzo, V.
通讯作者：
Di Marzo, V.
DOI：
10.1016/s0165-1838(99)00101-0
发表时间：
2000-03-15
期刊：
JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM
影响因子：
--
作者：
Cano, G;Card, JP;Sved, AF
通讯作者：
Sved, AF
影响因子：
5.5
作者：
Di, S;Boudaba, C;Tasker, JG
通讯作者：
Tasker, JG
影响因子：
2.5
作者：
Glatzer, NR;Hasney, CP;Smith, BN
通讯作者：
Smith, BN
影响因子：
4.8
作者：
Evanson, Nathan K.;Tasker, Jeffrey G.;Herman, James P.
通讯作者：
Herman, James P.