Ewa Bromek1, Marta Rysz1, Anna Haduch1, Władysława A Daniel2. 1. Maj Institute of Pharmacology, Department of Pharmacokinetics and Drug Metabolism, Polish Academy of Sciences, Kraków, Poland. 2. Maj Institute of Pharmacology, Department of Pharmacokinetics and Drug Metabolism, Polish Academy of Sciences, Kraków, Poland. Electronic address: nfdaniel@cyf-kr.edu.pl.
Abstract
BACKGROUND: Our previous study has demonstrated that activation of the 5-HT2, but not 5-HT1 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-HT2C serotonin receptor subtype in the ARC is engaged in the regulation of liver cytochrome P450. METHODS: The 5-HT2C serotonin receptor agonist CP-809,101 was injected into the ARC for 5 days. The liver cytochrome P450 activity and protein level were measured. RESULTS: In rats receiving an injection of the 5-HT2C 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. CONCLUSIONS: The obtained results suggest that the 5-HT2C 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-HT2C receptor present in the ARC.
BACKGROUND: Our previous study has demonstrated that activation of the 5-HT2, but not 5-HT1 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-HT2C serotonin receptor subtype in the ARC is engaged in the regulation of liver cytochrome P450. METHODS: The 5-HT2C serotonin receptor agonist CP-809,101 was injected into the ARC for 5 days. The liver cytochrome P450 activity and protein level were measured. RESULTS: In rats receiving an injection of the 5-HT2C 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. CONCLUSIONS: The obtained results suggest that the 5-HT2C 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-HT2C receptor present in the ARC.
Authors: Anna Haduch; Ewa Bromek; Marta Rysz; Renata Pukło; Mariusz Papp; Piotr Gruca; Magdalena Łasoń; Monika Niemczyk; Władysława A Daniel Journal: Pharmacol Rep Date: 2020-08-03 Impact factor: 3.024