Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat

Nissinen, Erkki; Lindén, Inge‐Britt; Schultz, Eija; Kaakkola, Seppo; Männistö, Pekka T.; Pohto, P

doi:10.1016/0014-2999(88)90614-0

Cited by 109 publications

(55 citation statements)

References 11 publications

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“…In the striatal tissue the linear formation of COMT products agreed with our earlier method (Reenilä et al, 1995). In addition, entacapone, a specifi c COMT inhibitor (Nissinen et al, 1988) with low nanomolar K i value (2.0 nM, Lotta et al, 1995), inhibited the formation of COMT products and confi rmed that the COMT reaction performed correctly. While entacapone blocked the formation of COMT products totally, SAH concentration was decreased by only 60% of the initial concentration.…”

Section: Discussionsupporting

confidence: 76%

Simultaneous analysis of catechol‐O‐methyl transferase activity, S‐adenosylhomocysteine and adenosine

Reenilä

Rauhala

2009

Biomedical Chromatography

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Novel HPLC method utilizing UV-detection was developed to analyse catechol-O-methyltransferase (COMT) products, vanillic acid and isovanillic acid, S-adenosylhomocysteine (SAH) and adenosine formed from dihydroxybenzoic acid and S-adenosyl-L-methionine (SAM) by incubation of the rat tissues. Entacapone, a COMT inhibitor, prevented the formation of SAH only partially in the striatal homogenate whereas in the kidney homogenate the increase of SAH was prevented by entacapone. In conclusion, this method was reliable, rapid and simple. COMT seemed to be partially responsible on the SAM utilizing methylations in the striatal homogenates while in the high COMT activity tissue, COMT was the main SAH producing methyltransferase.

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Section: Discussionsupporting

confidence: 76%

Simultaneous analysis of catechol‐O‐methyl transferase activity, S‐adenosylhomocysteine and adenosine

Reenilä

Rauhala

2009

Biomedical Chromatography

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“…2f ). In particular, the enzymatic formation of a [ 3 H]NADA-like compound from tyrosine was reduced when inhibiting tyrosine ␤-hydroxylase (21). More detailed studies are necessary to understand the biosynthesis of NADA in intact neurons.…”

Section: Resultsmentioning

confidence: 99%

An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors

Huang

Bisogno²,

Trevisani³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

882

729

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The vanilloid receptor VR1 is a nonselective cation channel that is most abundant in peripheral sensory fibers but also is found in several brain nuclei. VR1 is gated by protons, heat, and the pungent ingredient of ''hot'' chili peppers, capsaicin. To date, no endogenous compound with potency at this receptor comparable to that of capsaicin has been identified. Here we examined the hypothesis, based on previous structure-activity relationship studies and the availability of biosynthetic precursors, that N-arachidonoyl-dopamine (NADA) is an endogenous ''capsaicin-like'' substance in mammalian nervous tissues. We found that NADA occurs in nervous tissues, with the highest concentrations being found in the striatum, hippocampus, and cerebellum and the lowest concentrations in the dorsal root ganglion. We also gained evidence for the existence of two possible routes for NADA biosynthesis and mechanisms for its inactivation in rat brain. NADA activates both human and rat VR1 overexpressed in human embryonic kidney (HEK)293 cells, with potency (EC50 Ϸ 50 nM) and efficacy similar to those of capsaicin. Furthermore, NADA potently activates native vanilloid receptors in neurons from rat dorsal root ganglion and hippocampus, thereby inducing the release of substance P and calcitonin gene-related peptide (CGRP) from dorsal spinal cord slices and enhancing hippocampal paired-pulse depression, respectively. Intradermal NADA also induces VR1-mediated thermal hyperalgesia (EC50 ‫؍‬ 1.5 ؎ 0.3 g). Our data demonstrate the existence of a brain substance similar to capsaicin not only with respect to its chemical structure but also to its potency at VR1 receptors. V anilloid receptors of type 1 (VR1) are nonselective cation channels, expressed in peripheral sensory C and A␦ fibers and gated by nociceptive stimuli such as low pH, heat, and some plant toxins, of which capsaicin, the pungent principle of chili peppers, is the best known example (1-4). Evidence obtained by several laboratories and using different techniques (5-10) showed that VR1 is present also in the central nervous system, where it is unlikely to be the target of noxious heat and low pH, thus suggesting the existence of brain endogenous agonists for this receptor (11). Indeed, lipid mediators previously known to serve other functions in the brain, i.e., the endocannabinoid anandamide and some lipoxygenase derivatives, activate VR1, albeit with a potency considerably lower than that of capsaicin (12)(13)(14). The antinociceptive effects of VR1 blockers in two models of inflammatory hyperalgesia (15, 16) suggest that ''endovanilloids'' might be produced also by peripheral tissues and act in concert with locally enhanced temperature and acidity during inflammation.If an endovanilloid did exist, what would be the structural prerequisites that would allow for an optimal interaction with vanilloid receptors? Structure-activity relationship studies for vanilloid receptors have indicated that both the vanillyl-amine moiety and a long, unsaturated acyl chain are necessary to...

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“…On the other hand, some researchers suggest that CA and DHCA methylation into FA and DHFA respectively may occur in the gut (Booth et al 1957;Chesson et al 1999;Ranganathan & Ramasarma, 1974). In both rats and human subjects, dietary plant phenolics can undergo metabolism to form reactive intermediates by catechol-o-methyltransferases present in the liver, also in the kidneys and gastrointestinal tracts both stomach and intestine (Nissinen et al 1988;Schultz & Nissinen, 1989;Mannisto et al 1992). The lack of circulating levels of luteolin and apigenin could be due to their low concentrations in the test meal administered.…”

Section: Discussionmentioning

confidence: 99%

Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads ofCynara scolymusL. (cultivar Violetto di Provenza) in human subjects: a pilot study

et al. 2007

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The current growing interest for natural antioxidants has led to a renewed scientific attention for artichoke, due not only to its nutritional value, but, overall, to its polyphenolic content, showing strong antioxidant properties. The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides. In vitro studies, using cultured rat hepatocytes, have shown its hepatoprotective functions and in vivo studies have shown the inhibition of cholesterol biosynthesis in human subjects. Several studies have shown the effect on animal models of artichoke extracts, while information on human bioavailability and metabolism of hydroxycinnamates derivatives is still lacking. Results showed a plasma maximum concentration of 6·4 (SD 1.8) ng/ml for chlorogenic acid after 1 h and its disappearance within 2 h (P, 0·05). Peak plasma concentrations of 19·5 (SD6·9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6·4 (SD1·5) ng/ml and 8·4 (SD4·6) ng/ml within 1 h and after 8 h respectively. We observed a significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 h (P,0·05). No circulating plasma levels of luteolin and apigenin were present. Our study confirms the bioavailability of metabolites of hydroxycinnamic acids after ingestion of cooked edible Cynara scolymus L. (cultivar Violetto di Provenza).

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Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat

Cited by 109 publications

References 11 publications

Simultaneous analysis of catechol‐O‐methyl transferase activity, S‐adenosylhomocysteine and adenosine

Simultaneous analysis of catechol‐O‐methyl transferase activity, S‐adenosylhomocysteine and adenosine

An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors

Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads ofCynara scolymusL. (cultivar Violetto di Provenza) in human subjects: a pilot study

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