Dear Martino,

The following publications cover the answer to your question:

1-Proc Natl Acad Sci U S A. 2003 May 13; 100(10): 6186–6191.

Published online 2003 Apr 25. doi:  10.1073/pnas.0931309100

PMCID: PMC156347 (see attached file)

Neuroscience

Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine

Venkata S. Mattay, Terry E. Goldberg, Francesco Fera, Ahmad R. Hariri, Alessandro Tessitore, Michael F. Egan,Bhaskar Kolachana, Joseph H. Callicott, and Daniel R. Weinberger*

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ABSTRACT

Monamines subserve many critical roles in the brain, and monoaminergic drugs such as amphetamine have a long history in the treatment of neuropsychiatric disorders and also as a substance of abuse. The clinical effects of amphetamine are quite variable, from positive effects on mood and cognition in some individuals, to negative responses in others, perhaps related to individual variations in monaminergic function and monoamine system genes. We explored the effect of a functional polymorphism (val158-met) in the catecholO-methyltransferase gene, which has been shown to modulate prefrontal dopamine in animals and prefrontal cortical function in humans, on the modulatory actions of amphetamine on the prefrontal cortex. Amphetamine enhanced the efficiency of prefrontal cortex function assayed with functional MRI during a working memory task in subjects with the high enzyme activity val/val genotype, who presumably have relatively less prefrontal synaptic dopamine, at all levels of task difficulty. In contrast, in subjects with the low activity met/met genotype who tend to have superior baseline prefrontal function, the drug had no effect on cortical efficiency at low-to-moderate working memory load and caused deterioration at high working memory load. These data illustrate an application of functional neuroimaging in pharmacogenomics and extend basic evidence of an inverted-“U” functional-response curve to increasing dopamine signaling in the prefrontal cortex. Further, individuals with the met/met catechol O-methyltransferase genotype appear to be at increased risk for an adverse response to amphetamine.

2-Drug Metab Dispos. 2010 Oct; 38(10): 1892–1899.

doi:  10.1124/dmd.110.033548

PMCID: PMC2957166 (see attached file).

O-Methylation of Catechol Estrogens by Human Placental Catechol-O-Methyltransferase: Interindividual Differences in Sensitivity to Heat Inactivation and to Inhibition by Dietary Polyphenols

Bao Ting Zhu, Karen Y. Wu,1 Pan Wang, May Xiaoxin Cai, and Allan H. Conney

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Abstract

The human catechol-O-methyltransferase (COMT) is a polymorphic enzyme that catalyzes the O-methylation of catechol estrogens. Recent animal studies showed that placental COMT is involved in the development of placentas and embryos, probably via the formation of 2-methoxyestradiol. In this study, we analyzed a total of 36 human term placentas to determine their cytosolic COMT activity for the O-methylation of catechol estrogens as well as their sensitivity to inhibition by heat and dietary compounds. Large variations (up to 4-fold) in the COMT activity for the formation of methoxyestrogens were noted with different human placental samples. The cytosolic COMTs in different human placentas also displayed considerable differences in their sensitivity to heat inactivation. This differential sensitivity was not associated with the overall catalytic activity for the O-methylation of catechol estrogen substrates. It was observed that there was a positive correlation (r = 0.760) between the sensitivity of the human placental COMT to heat inactivation and its sensitivity to inhibition by (−)-epigallocatechin-3-gallate (a well known tea polyphenol with COMT-inhibiting activity) but an inverse correlation (r = 0.544) between heat inactivation and inhibition by quercetin (another dietary COMT inhibitor). The differences in inhibition by these two dietary compounds are due to different mechanisms of COMT inhibition involved.

3-CNS Neurol Disord Drug Targets. Author manuscript; available in PMC 2015 Mar 2.

Published in final edited form as:

CNS Neurol Disord Drug Targets. 2012 May; 11(3): 236–250.

PMCID: PMC4345409

NIHMSID: NIHMS666636 (see attached file).

The Role of the Catechol-O-Methyltransferase (COMT) Gene in Personality and Related Psychopathological Disorders

Christian Montag,1,2,3,* Magdalena Jurkiewicz,4 and Martin Reuter1,2,3

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Abstract

This review provides a short overview of the most significant biologically oriented theories of human personality. Personality concepts of Eysenck, Gray and McNaughton, Cloninger and Panksepp will be introduced and the focal evidence for the heritability of personality will be summarized. In this context, a synopsis of a large number of COMT genetic association studies (with a focus on the COMT Val158Met polymorphism) in the framework of the introduced biologically oriented personality theories will be given. In line with the theory of a continuum model between healthy anxious behavior and related psychopathological behavior, the role of the COMT gene in anxiety disorders will be discussed. A final outlook considers new research strategies such as genetic imaging and epigenetics for a better understanding of human personality.

4- Oxidative Medicine and Cellular Longevity

Volume 2016 (2016), Article ID 4251912, 17 pages

http://dx.doi.org/10.1155/2016/4251912 (see attached file).

Review Article

Redox Control of Multidrug Resistance and Its Possible Modulation by Antioxidants

Aysegul Cort,1 Tomris Ozben,2 Luciano Saso,3 Chiara De Luca,4 and Liudmila Korkina5

1Department of Nutrition and Dietetics, Faculty of Health Sciences, Sanko University, İncili Pınar, Gazi Muhtar Paşa Bulvarı, Sehitkamil, 27090 Gaziantep, Turkey

2Department of Biochemistry, Akdeniz University Medical Faculty, Campus, Dumlupınar Street, 07070 Antalya, Turkey

3Department of Physiology and Pharmacology “Vittorio Erspamer”, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy

4Evidence-Based Well-Being (EB-WB) Ltd., 31 Alt-Stralau, 10245 Berlin, Germany

5Centre of Innovative Biotechnological Investigations Nanolab, 197 Vernadskogo Prospekt, Moscow 119571, Russia

Received 12 August 2015; Revised 14 November 2015; Accepted 18 November 2015

Academic Editor: Sidhartha D. Ray

Copyright © 2016 Aysegul Cort et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Clinical efficacy of anticancer chemotherapies is dramatically hampered by multidrug resistance (MDR) dependent on inherited traits, acquired defence against toxins, and adaptive mechanisms mounting in tumours. There is overwhelming evidence that molecular events leading to MDR are regulated by redox mechanisms. For example, chemotherapeutics which overrun the first obstacle of redox-regulated cellular uptake channels (MDR1, MDR2, and MDR3) induce a concerted action of phase I/II metabolic enzymes with a temporal redox-regulated axis. This results in rapid metabolic transformation and elimination of a toxin. This metabolic axis is tightly interconnected with the inducible Nrf2-linked pathway, a key switch-on mechanism for upregulation of endogenous antioxidant enzymes and detoxifying systems. As a result, chemotherapeutics and cytotoxic by-products of their metabolism (ROS, hydroperoxides, and aldehydes) are inactivated and MDR occurs. On the other hand, tumour cells are capable of mounting an adaptive antioxidant response against ROS produced by chemotherapeutics and host immune cells. The multiple redox-dependent mechanisms involved in MDR prompted suggesting redox-active drugs (antioxidants and prooxidants) or inhibitors of inducible antioxidant defence as a novel approach to diminish MDR. Pitfalls and progress in this direction are discussed.

5-Int. J. Dev. Biol. 58: 247-259 (2014)

doi: 10.1387/ijdb.140083ms

Adaptive mechanisms controlling uterine spiral artery remodeling during the establishment of pregnancy (see attached file).

MICHAEL J. SOARES*, DAMAYANTI CHAKRABORTY, KAIYU KUBOTA,

STEPHEN J. RENAUD and M.A. KARIM RUMI

Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine,

University of Kansas Medical Center, Kansas City, Kansas, USA

ABSTRACT Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remodeling directed by maternal natural killer cells and embryo-derived invasive trophoblast lineages. The placentation site, including

remodeling of the uterine spiral arteries, is shaped by environmental challenges. In this review, we discuss the cellular participants controlling pregnancy-dependent uterine spiral artery remodeling and mechanisms responsible for their development and function.

Hoping this will be helpful,

Rafik

 Dear Rafik,

many thanks for your prompt reply. I am aware of the articles you quoted. However, these are all oriented on the dopamine or oestrogen metabolism rather than catecholamine's. Moreover I would like to know what modifies the activity of the enzyme other than the val-met mutation.