Topic
Catechol-O-methyl transferase
About: Catechol-O-methyl transferase is a research topic. Over the lifetime, 1646 publications have been published within this topic receiving 87360 citations.
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TL;DR: The results suggest that catechol‐O‐methyltransferase (COMT) is synthesized by cultured astrocytes, oligodendrocyts and neurons, and is localized and molecular forms in primary cultures, where cell types can be easily distinguished with specific markers.
38 citations
TL;DR: It is concluded that inhibition of MAO selectively increases RIF 5-HT, and catechol-O-methyltransferase appears to be more important than MAO in the metabolism of intrarenal DA.
Abstract: The purpose of the present investigation was to study the effects of inhibition of monoamine oxidase (MAO) and/or catechol-O-methyltransferase (COMT), enzymes involved in the degradation of dopamine (DA) and serotonin (5-HT), on intrarenal DA and 5-HT, as reflected in the renal interstitial fluid (RIF) microdialysate and urine, and on renal function. Inhibition of MAO selectively increased RIF 5-HT from 3.16 +/- 0.38 to 8.03 +/- 1.83 pg/min (n = 7, P < 0.05), concomitant with decreases in mean arterial blood pressure and glomerular filtration rate (2.09 +/- 0. 18 to 1.57 +/- 0.22 ml/min, n = 7, P < 0.05). Inhibition of COMT significantly increased RIF DA (3.47 +/- 0.70 to 8.68 +/- 1.96 pg/min, n = 9, P < 0.05), urinary DA (2.00 +/- 0.16 to 2.76 +/- 0.26 ng/min, n = 9, P < 0.05), and absolute excretion of sodium (6.42 +/- 2.00 to 9.82 +/- 1.62 micromol/min, n = 10, P < 0.05). Combined inhibition of MAO and COMT significantly increased RIF DA, urinary DA, and urinary 5-HT, which was accompanied with increases in urine flow rate, and absolute (3.03 +/- 0.59 to 8.40 +/- 1.61 micromol/min, n = 9, P < 0.01) and fractional excretion of sodium. We conclude that inhibition of MAO selectively increases RIF 5-HT. COMT appears to be more important than MAO in the metabolism of intrarenal DA. Physiological increases in intrarenal DA/5-HT induced by inhibition of their degrading enzymes are accompanied with significant alterations of renal function.
37 citations
TL;DR: In clinical trials, adjuvant treatment with entacapone appeared to be an effective and well-tolerated therapeutic strategy in patients with Parkinson's disease who experience fluctuations in the response to levodopa therapy.
37 citations
TL;DR: Findings provided convincing evidence that epistasis between the COMT and ALDH3B1 genes plays an important role in the pathogenesis of schizophrenia.
37 citations
TL;DR: ComT over expression or treatment with 2ME stabilize microtubules, ameliorates E2-induced proliferation, inhibits ERα and PR signaling, and reduces HIF-1 α and CYP19 expression in human uterine leiomyoma cells, indicating microtubule-targeting agent 2ME is a candidate target for treatment of uterineLeiomyomas.
Abstract: Context: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-Omethyltransferase (COMT). Our previous study demonstrated that 2ME is a potent antiproliferative, proapoptotic, antiangiogenic, and collagen synthesis inhibitor in human leiomyomas cells (huLM). Objectives: Our objectives were to investigate whether COMT expression, by the virtue of 2ME formation, affects the growth of huLM, and to explore the cellular and molecular mechanisms whereby COMT expression or treatment with 2ME affect these cells. Results: Our data demonstrated that E2-induced proliferation was less pronounced in cells over-expressing COMT or treated with 2ME (500 nM). This effect on cell proliferation was associated with microtubules stabilization and diminution of estrogen receptor a (ERa) and progesterone receptor (PR) transcriptional activities, due to shifts in their subcellular localization and sequestration in the cytoplasm. In addition, COMT over expression or treatment with 2ME reduced the expression of hypoxia-inducible factor -1a (HIF-1 a) and the basal level as well as TNF-a-induced aromatase (CYP19) expression. Conclusions: COMT over expression or treatment with 2ME stabilize microtubules, ameliorates E2-induced proliferation, inhibits ERa and PR signaling, and reduces HIF-1 a and CYP19 expression in human uterine leiomyoma cells. Thus, microtubules are a candidate target for treatment of uterine leiomyomas. In addition, the naturally occurring microtubuletargeting agent 2ME represents a potential new therapeutic for uterine leiomyomas.
37 citations