The role of central 5-HT3 receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats
The role of central 5-HT3 receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats
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DOI：
10.1113/jphysiol.2005.085845
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发表时间：
2005-08-01
影响因子：
5.5
通讯作者：
Jordan, D
中科院分区：
文献类型：
--
作者：
Jeggo, RD;Kellett, DO;Jordan, D
脑干5-羟色胺(5-羟色胺，5-羟色胺)神经元调节心血管反射反应，但许多5-羟色胺受体的不同作用尚未得到深入研究。本实验在麻醉大鼠上观察了5-HT3受体在调节孤束核(NTS)神经元迷走传入活动中的作用。记录来自301个NTS神经元，从刺激迷走神经获得长(>；20ms)最小起效潜伏期的输入。其中140个神经元由右房注射苯双胍(PBG)激活非髓鞘心肺传入。应用高选择性5-HT3受体激动剂PBG可显著增强96个受试神经元和17个受试神经元的电活动(从2.4+/-0.4个至5.5+/-0.8个S峰(-1))，而选择性5-HT3受体拮抗剂格拉司琼可显著减弱(3.4+/-1.1个至7.0+/-11.9个峰S(-1))的活动(3.0+/-0.9个至3.8+/-1个峰S(-1))。在10个受试者中，有9个神经元对迷走神经和心肺传入刺激的反应增强，而格拉司琼显著减弱这种心肺传入(20.2+/-5.7至10.6+/-4.1峰爆发(-1))。电泳法应用AMPA和NMDA也可兴奋NTS神经元，这种兴奋可分别被非NMDA受体拮抗剂DNQX和AP-5选择性拮抗。在这些选择性电流下，DNQX和AP-5也可减弱PBG和心肺输入引起的NTS活动的增加。这些数据与迷走神经输入，包括到NTS的非髓鞘心肺输入，利用含有5-羟色胺的途径激活5-HT3受体的假设一致。这种对5-HT3受体激活的兴奋性反应可能部分是直接的突触后作用，但也可能是由于谷氨酸的促进释放，谷氨酸反过来作用于非NMDA或NMDA受体来引起兴奋。
Brainstem 5-hydroxytryptamine (5-HT, serotonin)-containing neurones modulate cardiovascular reflex responses but the differing roles of the many 5-HT receptors have not been thoroughly investigated. The present experiments on anaesthetized rats investigated the role of 5-HT3 receptors in modulating vagal afferent evoked activity of nucleus tractus solitarius (NTS) neurones. Recordings were made from 301 NTS neurones receiving an input at long (>20 ms) minimum onset latency from stimulation of the vagus nerve. These included 140 neurones excited by activating non-myelinated cardiopulmonary afferents by right atrial injection of phenylbiguanide (PBG). lonophoretic application of PBG, a highly selective 5-HT3 receptor agonist, significantly increased activity (from 2.4 +/- 0.4 to 5.5 +/- 0.8 spikes s(-1)) in 96 of 106 neurones tested and in all 17 neurones tested the increase in activity (3.4 +/- 1.1 to 7.0 +/- 11.9 spikes s(-1)) was significantly attenuated (3.0 +/- 0.9 to 3.8 +/- 1.1 spikes s(-1)) by the selective 5-HT3 receptor antagonist granisetron. lonophoretic application of PBG potentiated responses to vagus nerve and cardiopulmonary afferent stimulation, and granisetron significantly attenuated this cardiopulmonary input (20.2 +/- 5.7 to 10.6 +/- 4.1 spikes burst(-1)) in 9 of 10 neurones tested. lonophoretic application of AMPA and NMDA also excited NTS neurones and these excitations could be selectively antagonized by the non-NMDA and NMDA receptor antagonists DNQX and AP-5, respectively. At these selective currents, DNQX and AP-5 also attenuated PBG- and cardiopulmonary input-evoked increases in NTS activity. These data are consistent with the hypothesis that vagal inputs, including non-myelinated cardiopulmonary inputs to the NTS, utilize a 5-HT-containing pathway which activates 5-HT3 receptors. This excitatory response to 5-HT3 receptor activation may be partly a direct postsynaptic action but part may also be due to facilitation of the release of glutamate which in turn acts on either non-NMDA or NMDA receptors to evoke excitation.