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Showing papers on "Catechol-O-methyl transferase published in 1977"


Journal Article
TL;DR: Catechol-O-methyltransferase activity was measured in blood obtained from 373 randomly selected subjects aged 16-18, 262 consecutive adult blood donors, and 201 first-degree relatives of subjects with RBC COMT activity of less than 8 U and the results of segregation analyses of the data were compatible with autosomal recessive inheritence of an allele for low RBCCOMT activity.
Abstract: Catechol-O-methyltransferase activity was measured in blood obtained from 373 randomly selected subjects aged 16-18, 262 consecutive adult blood donors, and 201 first-degree relatives of subjects with RBC COMT activity of less than 8 U. The distribution of RBC COMT activity in a randoly selected populations was apparently bimodal with a nadir at approximately 8 U. Of a randomly selected population, 23% had low RBC COMT activity (less than 8 U), Because of previous reports of a significant sibling-sibling correlation of RBC COMT activity and because of the presence of a subgroup of subjects with low enzyme activity, RBC COMT activity was measured in blood from first-degree relatives of probands with low erythrocyte enzyme activity in 48 families. The results of segregation analyses of the data were compatible with autosomal recessive inheritence of an allele for low RBC COMT activity. RBC COMT in blood samples from siblings of probands inthese families also showed an apparent biomodal distribution.

249 citations


Journal ArticleDOI
TL;DR: A sensitive simple radiometric method for the simultaneous measurement of norepinephrine, epinephrine, and dopamine is described and no cross-reactivity was noted for several compounds related to these catecholamines.

173 citations


Journal ArticleDOI
TL;DR: The result indicates that the decrease in tissue levels of S-Adenosylmethionine in organs of senescent rats is due to the increased utilization rather than the decreased synthesis of this methyl donor compound.
Abstract: The tissue levels of S-Adenosylmethionine (SAMe) in 30-mo.-old rats were measured, and a remarkable decrease was observed compared to adult rats. The synthesis of SAMe by the methionine-activating enzyme and its utilization by COMT were investigated in different tissues. The activity of the synthesizing enzyme was unchanged in the liver and brain of adult and senescent rats, while COMT activity appeared to be higher in the aging rats. Thus, the result indicates that the decrease of same in these organs of senescent rats is due to the increased utilization rather than the decreased synthesis of this methyl donor compound.

63 citations


Journal ArticleDOI
TL;DR: Results from the present study demonstrate that the solubilized, partially purified enzyme is similar to the cytosol COMT with respect to molecular weight, pH profile, sensitivity toward inhibitors, Mg2+ requirement, and substrate affinities, but a comparison of the crude particulate COMT and the Solubilization shows that there is a significant difference in their affinity for catechol substrates.
Abstract: Particulate catechol-O-methyltransferase (COMT) from rat liver has been solubilized by acetone treatment and partially purified Results from the present study demonstrate that the solubilized, partially purified enzyme is similar to the cytosol COMT with respect to molecular weight, pH profile, sensitivity toward inhibitors, Mg2+ requirement, and substrate affinities However, a comparison of the crude particulate COMT and the solubilized enzyme shows that there is a significant difference in their affinity for catechol substrates This finding suggests that membrane protein and (or) lipid components may play an important role in catecholamine metabolism The relationship of particulate COMT to [3H]norepinephrine binding was investigated No correlation between the COMT and [3H]norepinephrine binding activities was observed in vitro

40 citations


Journal Article
TL;DR: The results show that the suppressed behavioral activity seen in lithium-treated hyperthyroid rats may be associated with decreased synthesis of norepinephrine and dopamine in the brain.
Abstract: Daily treatment of neonatal rats with 1-triiodothyronine for 30 days increased locomotor activity as well as the synthesis and presumably, release of brain norepinephrine, dopamine and 5-hydroxytryptamine. Whereas administration of lithium carbonate (60 mg/kg) to normal rats for 10 days, beginning from the 20th day of age, produced no significant effect, this antimanic drug significantly decreased the observed increase in spontaneous locomotor activity in l-triiodothyronine-treated rats. Lithium treatment in normal rats increased the activity of striatal tyrosine hydroxylase, but produced no significant effect on the endogenous levels of norepinephrine and dopamine in several discrete brain regions examined. Lithium, enhanced deamination of catecholamines as evidenced by increased level of 3,4-dihydroxyphenylacetic acid and monoamine oxidase activity in normal rats. The activity of catechol o-methyltransferase was decreased to 82 and 59% in midbrain and crebral cortex of normal rats, respectively. Furthermore, chronic treatment with lithium increased endogenous levels of tryptophan, tryptophan hydroxylase, 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, in normal animals. In contrast to the effects seen in normal rats, admininstration of lithium in l-triiodothyronine-treated animals significantly decreased tyrosine hydroxylase as well as dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid, suggesting that this antimanic drug reduced the synthesis and turnover of dopamine. However, the steady-state levels of norepinephrine were raised in hypothalamus, pons-medulla, midbrain and striatum of lithium-treated hyperthyroid rats. As seen in normal animals, lithium in l-triidothyronine-treated rats increased trytophan, tryptophan hydroxylase and 5-hydroxytryptamine levels, but decreased the concentration of 5-hydroxyindoleacetic acid. The results show that the suppressed behavioral activity seen in lithium-treated hyperthyroid rats may be associated with decreased synthesis of norepinephrine and dopamine in the brain. Finally, the effects exerted by lithium on the brain catecholamine metabolizing system of young hyperthyroid rats were not similar to those seen in normal rats of the corresponding age group.

19 citations


Journal ArticleDOI
TL;DR: ComT activity of the superior cervical ganglion, pineal gland and anterior hypophysis did not exhibit significant changes after any of the hormone schedules used, and no differences in enzyme activity were observed between hormone- and vehicle-injected controls.
Abstract: The effect of estradiol and testosterone on the activity of catechol-O- methyl transferase (COMT) of the superior cervical ganglion, pineal gland, anterior hypophysis and hypothalamus were examined in castrated rats. In female rats a single injection of 2 mug of estradiol caused a significant 25% increase of hypothalamic COMT, whereas after 3 daily injections no differences in enzyme activity were observed between hormone- and vehicle-injected controls. In male rats testosterone propionate (0.5 mg) increased hypothalamic COMT by 53%; this effect was not detectable in animals treated with the androgen for 3 days. COMT activity of the superior cervical ganglion, pineal gland and anterior hypophysis did not exhibit significant changes after any of the hormone schedules used.

13 citations


Journal Article
TL;DR: The levels of norepinephrine, dopamine and 5-hydroxytryptamine in brain homogenates of vitamin B12-deficient rats have been investigated and both acetyl cholinesterase and butiryl-cholinestersterase markedly decreased in the plasma of the vitamin B 12-deficiency rats.
Abstract: The levels of norepinephrine, dopamine and 5-hydroxytryptamine in brain homogenates of vitamin B12-deficient rats have been investigated. The norepinephrine levels were significantly decreased in the deficient animals compared to controls. The two major catabolic pathways of norepinephrine e.g. monoamine oxidase and catechol-O-methyl transferase did not show significant variations. Both acetyl cholinesterase and butiryl-cholinesterase markedly decreased in the plasma of the vitamin B12-deficient rats.

10 citations


Journal ArticleDOI
TL;DR: NBG is potent both in vitro (Ki 1.7 × lO −6 M) and in vivo (complete blockade of HVA rise with 50 mg/kg), but its duration of action is very short in vivo ($15–45 min.)

8 citations


Journal ArticleDOI
TL;DR: Platelet monoamine oxidase (MAO) and RBC catechol-O-methyltransferase (COMT) were studied in 12 women suffering from premenstrual syndrome and no significant variation of platelet MAO or RBC COMT was found during the menstrual cycle.
Abstract: Platelet monoamine oxidase (MAO) and RBC catechol-O-methyltransferase (COMT) were studied in 12 women suffering from premenstrual syndrome. No significant variation of platelet MAO or RBC COMT was fou

7 citations


Journal ArticleDOI
TL;DR: It is reached that benzimidazole and catechol are bioisosteric molecules and the implication of this in the pharmacology of adrenergic systems is discussed.

5 citations


Journal ArticleDOI
TL;DR: RO-4-4602, a peripheral L-DOPA decarboxylase inhibitor, was shown to also inhibit the activity of catechol O-methyltransferase (COMT) and is the most potent inhibitor of COMT yet known.
Abstract: RO-4-4602, a peripheral L-DOPA decarboxylase (EC 4.1.1.28) inhibitor was shown to also inhibit the activity of catechol O-methyltransferase (COMT) (EC 2.1.1.6). Kinetic study indicated that the inhibition is of a competitive nature. The apparent Ki values of 7 X 10(6), 5.3 X 10(-6, and 9 X 10-6) M calculated from Lineweaver-Burke plots when dopamine, norepinephrine, and epinephrine, respectively, were used as substrate, showed that this drug is the most potent inhibitor of COMT yet known.