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Serotonin Receptors of 5-HT; 2; Type in the Hypothalamic Arcuate Nuclei Positively Regulate Liver Cytochrome P450 via Stimulation of the Growth Hormone-Releasing Hormone/Growth Hormone Hormonal Pathway

Bromek, Ewa and Rysz, Marta and Haduch, Anna and Daniel, Władysława A.. (2019) Serotonin Receptors of 5-HT; 2; Type in the Hypothalamic Arcuate Nuclei Positively Regulate Liver Cytochrome P450 via Stimulation of the Growth Hormone-Releasing Hormone/Growth Hormone Hormonal Pathway. Drug Metabolism and Disposition, 47 (2). pp. 80-85.

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Official URL: https://edoc.unibas.ch/82362/

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Abstract

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-HT; 1; or 5-HT; 2; , 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-HT; 1; -type receptor agonist] or 2,5-dimethoxy-4-iodoamphetamine [(DOI), a 5-HT; 2; -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-HT; 2; , but not the 5-HT; 1; -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-HT; 2; receptor subtypes (5-HT; 2A; , 5-HT; 2B; , or 5-HT; 2C; ) is responsible for the observed neuroendocrine regulation of cytochrome P450.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Biopharmazie (Meyer zu Schwabedissen)
UniBasel Contributors:Rysz, Marta Anna
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Pharmacology and Experimental Therapeutics
ISSN:0090-9556
e-ISSN:1521-009X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Mar 2021 12:01
Deposited On:23 Mar 2021 12:01

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