PT  - JOURNAL ARTICLE
AU  - Bromek, Ewa
AU  - Rysz, Marta
AU  - Haduch, Anna
AU  - Daniel, Władysława A.
TI  - Serotonin Receptors of 5-HT<sub>2</sub> Type in the Hypothalamic Arcuate Nuclei Positively Regulate Liver Cytochrome P450 via Stimulation of the Growth Hormone–Releasing Hormone/Growth Hormone Hormonal Pathway
AID  - 10.1124/dmd.118.083808
DP  - 2019 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 80--85
VI  - 47
IP  - 2
4099  - http://dmd.aspetjournals.org/content/47/2/80.short
4100  - http://dmd.aspetjournals.org/content/47/2/80.full
SO  - Drug Metab Dispos2019 Feb 01; 47
AB  - Our recent study carried out after local injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine into the arcuate nucleus (ARC) of the hypothalamus suggested a positive influence of the serotonergic innervation of the ARC on growth hormone (GH) secretion and GH-dependent expression of cytochrome P450. The aim of our present study was to determine the effect of the activation of the serotonin (5-HT)-type receptors, 5-HT1 or 5-HT2, in the ARC on the expression and activity of cytochrome P450 in the liver of male rats. The serotonergic agonist 5-carboxyamidotryptamine [(5-CT), a 5-HT1-type receptor agonist] or 2,5-dimethoxy-4-iodoamphetamine [(DOI), a 5-HT2-type receptor agonist] was injected into the ARC for 5 days. The activity and expression of cytochrome P450 isoenzymes and the levels of serum and pituitary hormones were estimated. DOI significantly increased the activity and expression (both mRNA and protein levels) of CYP2C11, CYP3A1/23, and CYP3A2, which positively correlated with an increase in the pituitary growth hormone–releasing hormone (GHRH) and serum GH level. The injection of 5-CT into the ARC did not affect the activity of liver P450 enzymes or hormone levels. The obtained results indicate that 5-HT2, but not the 5-HT1-type receptors in the ARC, are engaged in the positive neuroendocrine regulation of cytochrome P450, possibly by the stimulation of hypothalamic GHRH release and pituitary GH secretion, and an increase in the serum GH concentration. Further studies are going to identify which of the 5-HT2 receptor subtypes (5-HT2A, 5-HT2B, or 5-HT2C) is responsible for the observed neuroendocrine regulation of cytochrome P450.