Wan Shuxia, Browning Kirsteen N, Coleman F Holly, Sutton Gregory, Zheng Hiyuan, Butler Andrew, Berthoud Hans-Rudolf, Travagli R Alberto
Key Laboratory of Allergy and Immune-Related Diseases, Department of Physiology, School of Basic Medical Science, Wuhan University, Wuhan 430071, Hubei, China.
J Neurosci. 2008 May 7;28(19):4957-66. doi: 10.1523/JNEUROSCI.5398-07.2008.
The nucleus tractus solitarius (NTS) integrates visceral sensory signals with information from the forebrain to control homeostatic functions, including food intake. Melanocortin 3/4 receptor (MC3/4R) ligands administered directly to the caudal brainstem powerfully modulate meal size but not frequency, suggesting the enhancement of visceral satiety signals. Using whole-cell recordings from rat brainstem slices, we examined the effects of melanocortin ligands, alpha-melanocyte-stimulating hormone (alphaMSH) and melanotan II (MTII), on EPSC in NTS neurons. Thirty-two percent of NTS neurons responded to perfusion with MTII or alphaMSH with either an increase (24%) or a decrease (8%) in the frequency, but not amplitude, of spontaneous EPSCs; the effects of MTII were abolished by pretreatment with SHU9119. After surgical vagal deafferentation, only four of 34 (9%) NTS neurons responded to MTII with an increase in EPSC frequency. When EPSCs were evoked by electrical stimulation of the tractus solitarius in Krebs' solution with 2.4 mm Ca(2+)(e), alphaMSH and MTII increased the amplitude in six of the 28 neurons tested, decreased amplitude in 14 with no effect in the remaining eight neurons. In four of six neurons unresponsive to MTII, decreasing Ca(2+)(e) levels to 1.5 mM uncovered an excitatory effect of MTII on EPSC amplitude. Reverse transcription-PCR analysis revealed the presence of MC4R, but not MC3R, in nodose ganglia. These results show that MC4R signaling leads mainly to presynaptic modulation of glutamatergic synaptic transmission and suggest that melanocortinergic-induced decrease of food intake may occur via enhancement of vagal afferent satiation signals from the gastrointestinal tract.
孤束核（NTS）将内脏感觉信号与来自前脑的信息整合起来，以控制包括食物摄入在内的稳态功能。直接给予脑干尾部的黑皮质素3/4受体（MC3/4R）配体可强烈调节进餐量，但不影响进餐频率，提示内脏饱腹感信号增强。我们使用大鼠脑干切片的全细胞膜片钳记录技术，研究了黑皮质素配体α-黑素细胞刺激素（αMSH）和二型促黑素（MTII）对NTS神经元兴奋性突触后电流（EPSC）的影响。32%的NTS神经元在灌注MTII或αMSH后，自发性EPSC的频率增加（24%）或降低（8%），但幅度不变；SHU9119预处理可消除MTII的作用。迷走神经切断术后，34个NTS神经元中只有4个（9%）对MTII产生EPSC频率增加的反应。当在含有2.4 mM Ca²⁺（e）的Krebs溶液中通过电刺激孤束诱发EPSC时，αMSH和MTII使28个受试神经元中的6个EPSC幅度增加，14个幅度降低，其余8个无影响。在6个对MTII无反应的神经元中，有4个将Ca²⁺（e）水平降至1.5 mM时，MTII对EPSC幅度产生兴奋作用。逆转录-聚合酶链反应分析显示，结状神经节中存在MC4R，但不存在MC3R。这些结果表明，MC4R信号传导主要导致谷氨酸能突触传递突触前调制，并提示黑皮质素能诱导的食物摄入量减少可能通过增强来自胃肠道的迷走神经传入饱腹感信号而发生。
