Wójcikowski Jacek, Daniel Władysława A
Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2008 Nov-Dec;60(6):966-71.
Our earlier study showed that damage to brain dopaminergic pathways causes decreases in CYP2B, CYP2C11 and CYP3A, as well as increases in CYP1A protein levels and activities in the liver. The aim of the present study was to investigate the influence of lesions of brain dopaminergic pathways on hormones and cytokines that are thought to mediate the effect of the dopaminergic system on liver CYP expression. At 48 h or 7 days after lesion of the tuberoinfundibular pathway, growth hormone level was significantly decreased, while the concentration of triiodothyronine was considerably increased. Fourteen days after lesion of the mesolimbic pathway, triiodothyronine level was significantly elevated, while corticosterone concentration was visibly reduced. The plasma levels of thyroxine, testosterone, interleukin-2, and interleukin-6 were not changed after lesion of the tuberoinfundibular or the mesolimbic pathways. The present study suggests that liver CYP is regulated by the dopaminergic tuberoinfundibular pathway via growth hormone and triiodothyronine, while the mesolimbic pathway influences this enzyme via corticosterone and triiodothyronine. Cytokines are not involved in the observed down-regulation of CYP isoforms after lesion of either dopaminergic pathway.
我们早期的研究表明,脑多巴胺能通路受损会导致肝脏中细胞色素P450 2B(CYP2B)、细胞色素P450 2C11(CYP2C11)和细胞色素P450 3A(CYP3A)减少,以及细胞色素P450 1A(CYP1A)蛋白水平和活性增加。本研究的目的是探讨脑多巴胺能通路损伤对激素和细胞因子的影响,这些激素和细胞因子被认为介导多巴胺能系统对肝脏CYP表达的作用。在结节漏斗通路损伤后48小时或7天,生长激素水平显著降低,而三碘甲状腺原氨酸浓度显著升高。在中脑边缘通路损伤后14天,三碘甲状腺原氨酸水平显著升高,而皮质酮浓度明显降低。在结节漏斗或中脑边缘通路损伤后,血浆甲状腺素、睾酮、白细胞介素-2和白细胞介素-6水平未发生变化。本研究表明,肝脏CYP受多巴胺能结节漏斗通路通过生长激素和三碘甲状腺原氨酸调节,而中脑边缘通路通过皮质酮和三碘甲状腺原氨酸影响该酶。细胞因子不参与任何一条多巴胺能通路损伤后观察到的CYP同工酶下调。