Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 23:16:737716.
doi: 10.3389/fnins.2022.737716. eCollection 2022.

Stress as a Potential Regulatory Factor in the Outcome of Pharmacotherapy

Maria Konstandi  1 , Elizabeth O Johnson  2 , Matti A Lang  3
Affiliations

Stress as a Potential Regulatory Factor in the Outcome of Pharmacotherapy

Maria Konstandi et al. Front Neurosci. .
No abstract available

Keywords: CYP2D6; CYP3A4; cytochrome; drug metabolism; pharmacotherapy; stress.

PubMed Disclaimer

Conflict of interest statement

ML was employed by Neomind Tech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the stress-induced neuroendocrine responses that presumably affect the regulation of the main drug-metabolizing cytochromes (CYP). Epinephrine and norepinephrine bind to adrenergic receptors (AR) in the periphery including hepatocytes, immune cells (stimulate release of cytokines), hepatic blood vessels (modify liver hemodynamics) and on pancreatic beta-cells (control insulin release positively via β2-ARs or negatively via α2-AR). Stress stimulates the secretion of norepinephrine in the hypothalamus that controls the release of several releasing factors regulating the secretion of hormones from the pituitary (Konstandi, ; Konstandi et al., 2014). The left side of the scheme indicates the effect of hypothalamic-pituitary-adrenal axis stimulation by stress on hepatic CYP regulation. CRH, corticotropin releasing hormone; GHRH, growth hormone releasing hormone; TRH, thyrotropin releasing hormone; PIF, prolactin inhibiting factor; GnRH, gonadotrophin releasing hormone; TSH, thyrotropin stimulating hormone; GH, growth hormone; T3, T4, thyroid hormones; ACTH, adrenocorticotropin hormone; PRL, prolactin; IR, insulin receptor; CytR, cytokine receptor; GHR, growth hormone receptor; TR, thyroid hormone receptor; GR, glucocorticoid receptor; SHR, steroid hormone receptor.
See this image and copyright information in PMC

References

    1. Anna Haduch A., Bromek E., Daniel W. A. (2013). Role of brain cytochrome P450 (CYP2D) in the metabolism of monoaminergic neurotransmitters. Pharmacol. Rep. 65, 1519–1528. 10.1016/S1734-1140(13)71513-5 - DOI - PubMed
    1. Arinc E., Arslan S., Adali O. (2005). Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver. Arch. Toxicol. 79, 427–433. 10.1007/s00204-005-0654-8 - DOI - PubMed
    1. Chen C.-S., Lin J. T., Goss K. A., He Y.-A., Halpert J. R., et al. (2004). Activation of the anticancer prodrugs cyclophosphamide and ifosfamide: identification of cytochrome P450 2B enzymes and site-specific mutants with improved enzyme kinetics. Mol. Pharmacol. 65, 1278–1285. 10.1124/mol.65.5.1278 - DOI - PubMed
    1. Chrousos G. P. (2009). Stress and disorders of the stress system. Nat. Rev. Endocrinol. 5, 374–381. 10.1038/nrendo.2009.106 - DOI - PubMed
    1. Chrousos G. P., Gold P. W. (1992). The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 267, 1244–1252. 10.1001/jama.267.9.1244 - DOI - PubMed

LinkOut - more resources