Manzke Till, Guenther Ulf, Ponimaskin Evgeni G, Haller Miriam, Dutschmann Mathias, Schwarzacher Stephan, Richter Diethelm W
Department of Neuro- and Sensory Physiology, University of Goettingen, Humboldtallee 23, 37073 Goettingen, Germany.
Science. 2003 Jul 11;301(5630):226-9. doi: 10.1126/science.1084674.
Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor-specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.
阿片类药物是麻醉学中广泛使用的镇痛药，但它们有严重的副作用，如呼吸抑制。这是由对脑干前包钦格复合体（PBC）中产生节律的呼吸神经元的直接抑制引起的。我们报告，5-羟色胺4(a) [5-HT4(a)]受体在呼吸PBC神经元中强烈表达，其选择性激活可保护自发呼吸活动。用5-HT4受体特异性激动剂治疗大鼠可克服芬太尼引起的呼吸抑制，并重新建立稳定的呼吸节律，而不会丧失芬太尼的镇痛效果。这些发现意味着通过神经元中汇聚的信号通路调节细胞内3',5'-环磷酸腺苷水平，有望从阿片类药物引起的呼吸抑制中实现微调恢复。
