Madden Christopher J, Morrison Shaun F
Neurological Sciences Institute/OHSU, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
J Physiol. 2006 Dec 1;577(Pt 2):525-37. doi: 10.1113/jphysiol.2006.116574. Epub 2006 Sep 14.
In urethane-chloralose anaesthetized, neuromuscularly blocked, ventilated rats, we examined the effects on sympathetic outflow to brown adipose tissue (BAT) of separate and simultaneous spinal microinjections of NMDA and serotonin. Microinjection of NMDA (12 pmol) into the right T4 spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak: +546% of control), BAT thermogenesis (+0.8 degrees C) and heart rate (+53 beats min-1), whereas microinjection of a lower dose of NMDA (1.2 pmol) did not change any of the recorded variables. Microinjection of 5-hydroxytryptamine (5-HT, 2 nmol) into the T4 IML increased BAT SNA (peak: +342% of control) at a long latency (mean onset: 23 min). The long latency 5-HT-evoked increase in BAT SNA was prevented by microinjection of methysergide (600 pmol) into the T4 IML. The increases in BAT SNA evoked by T4 IML microinjections of NMDA (12 pmol) were significantly potentiated (two to three times larger than the response to NMDA alone) following T4 IML microinjections of 5-HT (100 pmol to 2 nmol, but not 20 pmol). Also, microinjection of 5-HT (200 pmol) converted the subthreshold dose of NMDA (1.2 pmol) into an effective dose for increasing BAT SNA and heart rate. The 5-HT-mediated potentiation of the increase in BAT SNA evoked by microinjection of NMDA into the T4 IML was reversed by microinjection of methysergide (600 pmol) into the T4 IML. These results demonstrate that BAT SNA and thermogenesis can be driven by activation of spinal excitatory amino acid or 5-HT receptors and that concomitant activation of spinal NMDA and 5-HT receptors can act synergistically to markedly increase BAT SNA and thermogenesis.
在氨基甲酸乙酯-氯醛糖麻醉、神经肌肉阻断、机械通气的大鼠中，我们研究了分别及同时向脊髓微量注射N-甲基-D-天冬氨酸（NMDA）和5-羟色胺（5-羟色胺）对棕色脂肪组织（BAT）交感神经输出的影响。向右侧T4脊髓中间外侧核（IML）微量注射NMDA（12皮摩尔）可立即增加同侧棕色脂肪组织（BAT）交感神经活动（SNA；峰值：对照值的+546%）、BAT产热（+0.8摄氏度）和心率（+53次/分钟），而注射较低剂量的NMDA（1.2皮摩尔）则不会改变任何记录变量。向T4 IML微量注射5-羟色胺（5-HT，2纳摩尔）可在较长潜伏期（平均起效时间：23分钟）时增加BAT SNA（峰值：对照值的+342%）。向T4 IML微量注射麦角新碱（600皮摩尔）可阻止5-HT诱发的BAT SNA的长潜伏期增加。在向T4 IML微量注射5-HT（100皮摩尔至2纳摩尔，但不是20皮摩尔）后，向T4 IML微量注射NMDA（12皮摩尔）诱发的BAT SNA增加显著增强（比单独对NMDA的反应大两到三倍）。此外，微量注射5-HT（200皮摩尔）可将亚阈值剂量的NMDA（1.2皮摩尔）转变为增加BAT SNA和心率的有效剂量。向T4 IML微量注射麦角新碱（600皮摩尔）可逆转5-HT介导的向T4 IML微量注射NMDA诱发的BAT SNA增加的增强作用。这些结果表明，BAT SNA和产热可由脊髓兴奋性氨基酸或5-HT受体的激活驱动，并且脊髓NMDA和5-HT受体的同时激活可协同作用，显著增加BAT SNA和产热。
