Maj Institute of Pharmacology, Department of Pharmacokinetics and Drug Metabolism, Polish Academy of Sciences, Kraków, Poland.
Maj Institute of Pharmacology, Department of Pharmacokinetics and Drug Metabolism, Polish Academy of Sciences, Kraków, Poland.
Pharmacol Rep. 2019 Dec;71(6):1210-1212. doi: 10.1016/j.pharep.2019.05.010. Epub 2019 May 17.
Our previous study has demonstrated that activation of the 5-HT, but not 5-HT serotonin receptor type in the hypothalamic arcuate nucleus (ARC) is responsible for the neuroendocrine regulation of liver cytochrome P450. The goal of these studies was to determine whether 5-HT serotonin receptor subtype in the ARC is engaged in the regulation of liver cytochrome P450.
The 5-HT serotonin receptor agonist CP-809,101 was injected into the ARC for 5 days. The liver cytochrome P450 activity and protein level were measured.
In rats receiving an injection of the 5-HT serotonin receptor agonist CP-809,101 into the ARC (1 μg/side) for five days, the activities of CYP2B, CYP2C11 and CYP3A significantly increased corresponding with the elevated enzyme protein level.
The obtained results suggest that the 5-HT serotonin receptor subtype in the ARC is involved in the positive neuroendocrine regulation of cytochrome P450. Further studies are in progress to explain the physiological mechanism which is responsible for the observed regulation of cytochrome P450 by 5-HT receptor present in the ARC.
我们之前的研究表明，下丘脑弓状核（ARC）中 5-HT 的激活，而不是 5-HT 血清素受体类型，负责肝脏细胞色素 P450 的神经内分泌调节。这些研究的目的是确定 ARC 中的 5-HT 血清素受体亚型是否参与了肝脏细胞色素 P450 的调节。
将 5-HT 血清素受体激动剂 CP-809,101 注射到 ARC 中 5 天。测量肝细胞色素 P450 活性和蛋白水平。
在接受 5-HT 血清素受体激动剂 CP-809,101 注射到 ARC（1μg/侧）5 天的大鼠中，CYP2B、CYP2C11 和 CYP3A 的活性显著增加，相应的酶蛋白水平也升高。
所得结果表明，ARC 中的 5-HT 血清素受体亚型参与了细胞色素 P450 的正向神经内分泌调节。正在进行进一步的研究，以解释负责观察到的 ARC 中 5-HT 受体对细胞色素 P450 调节的生理机制。
