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PubMed1976

[Purification and properties of rat kidney catechol-O-methyltransferase].

The S-adenosyl-methionine: catechol-O-methyltransferase (EC 2.1.1.6) from rat kidney was purified about 650 fold as compared with the homogenate and the result of disc electrophoresis presented. The purification involved extraction, precipitation at pH 5, ammonium sulfate fractionation, Chromatographies on Biogel 0.5 m, Ultrogel AcA 44 and DE Sephadex A 50. Affinity chromatography was tried but unsuccessful. The enzyme exhibited two pH optima at 7.9 and 9.6 with a minimum at about 8.9. The COMT had a temperature optimum of 50 degrees C, with activation energy of 23.1 Kcal/Mole between 25-35 degrees C, 18.9 Kcal/mole between 35-45 degrees C and the Q10 within the range of 25-35 degrees amounted to 3.5. The molecular weight was estimated to be 21500+/-1000 daltons from its behavior on Ultrogel AcA 44 and the pH1 determined by electrofocalisation was near 5.50. The time of half life of the best purified enzymatic extract was found to be 2 h 10 min. at -20 degrees C. At basic pH the instability of the enzyme was increased. Since O-methylation required the presence of divalent cations, our results show that apparent Michaelis constants for Mg++ and Mn++ were respectively 0.50 X 10(-3) M and 0.33 X 10(-5) M. The study of their Hill's number indicated that there was only one point of fixation on the enzyme. The Km value determined by Florini and Vestling's method were 2.5 X 10(-4) M and 11.9 X 10(-5) M for epinephrine and S-adenosyl-methionine respectively. All results were discussed with respect to other investigations.

Animals↗
PubMed2025

The importance of dopamine levels and single-nucleotide polymorphism within COMT, DRD1 and DRD2 genes in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a prevalent sleep disorder that contributes to serious cardiovascular comorbidities. While the mechanical aspects of OSA are well-studied, its neurobiological underpinnings remain underexplored. In this study, we investigated the role of dopamine and its genetic modulators in OSA pathophysiology. PATIENTS AND METHODS: Serum dopamine levels were assessed in a cohort of 153 participants (96 OSA patients and 57 controls), and single-nucleotide polymorphisms (SNPs) in dopamine-related genes, including COMT, DRD1 and DRD2, were analysed in a cohort of 286 participants (141 OSA patients and 145 controls). RESULTS: Elevated serum dopamine levels were observed in OSA patients (p = 0.01), with dopamine levels correlating independently with OSA and male gender. Genotypic analysis identified the DRD2 rs1800497 T allele as a potential independent predictor of OSA severity (p = 0.011), hypopnea (p = 0.005) and arousals (p = 0.024). CONCLUSIONS: This study advances the understanding of OSA by identifying elevated dopamine levels and genetic variations in DRD2 rs1800497 as potential modulators of its occurrence and severity. These findings pave the way for personalized diagnostic and therapeutic approaches. By integrating neurobiology, genetics, and clinical practice, this research contributes to the evolving framework for precision medicine in sleep disorders.

Humans↗
PubMed1978

Evidence for the role of adrenocortical hormones in the regulation of noradrenaline and dopamine metabolism in certain brain areas.

1 Bilateral adrenalectomy suppressed body growth and increased the activity of tyrosine hydroxylase in rat striatum in a time-dependent manner. Fifteen days after adrenalectomy, the concentrations of noradrenaline were decreased significantly in hypothalamus and striatum, as were those of dopamine in brain stem and striatum. 2 Catechol-O-methyltransferase failed to change in response to adrenalectomy, but the activity of monoamine oxidase in cortex was significantly increased 7 days after surgery. These changes in various neurochemical parameters were even more pronounced 15 days after adrenal ablation. 3 Administration of corticosterone (10 mg/kg i.p.) to adrenalectomized rats effectively reversed the observed effects on brain amine metabolism. Corticosterone treatment for 7 days beginning from the 8th day of adrenalectomy virtually restored the concentrations of noradrenaline and dopamine as well as the activities of striatal tyrosine hydroxylase and cerebrocortical monoamine oxidase to the values seen for sham-operated controls. 4 Our data suggest that changes seen in brain noradrenaline and dopamine of adrenalectomized rats are specific to adrenocortical steroids and that these hormones play a role in the regulation of catecholamine formation.

Adrenal Cortex Hormones↗
PubMed1977

Monoamine oxidase and catechol-O-methyl transferase activity in Tetrahymena.

Tetrahymena pyriformis strain HSM was found to have monomine oxidase (MAO) and a catechol-3-methyl transferase-like (COMT) activity. As in mammalian tissues, the MAO activity is predominantly localized in the mitochondrial pellet and COMT in the cytosol. The COMT-like activity was present in amounts comparable to several mouse tissues and was inhibited by tropolone. MAO activity was much lower than in any of the mouse tissues tested, and its activity varied greatly from preparation to preparation. The substrate preference of Tetrahymena MAO was tryptamine greater than serotonin greater than dopamine, and activity increased with increasing pH from pH 6.5 to pH 7.8, as does that of mouse liver MAO. Teh Km of Tetrahymena MAO for tryptamine was approximately 4 micrometer, an order of magnitude lower than that of mouse liver MAO. Sensitivity of inhibition by MAO inhibitors was variable. In some preparations, no inhibition was observed. In others clear inhibition was obtained, harmine and clorgyline being among the most potent inhibitors.

Animals↗
PubMed1977

Lithium suppresses elevated behavioural activity and brain catecholamines in developing hyperthyroid rats.

Neonatal hyperthyroidism in rats induced by daily administration of L-triiodothyronine for 30 days since birth resulted in a significant rise in mobility and the metabolism of brain norepinephrine and dopamine. Whereas administration of lithium carbonate (60 mg/kg ip) to normal rats for 6 days produced no effect on spontaneous locomotor activity and increased the synthesis and possibly release of this monoamine in several brain regions, this antimanic drug antagonized the L-triiodothyronine-stimulated increases in mobility as well as norepinephrine and dopamine metabolism of hypothalamus, midbrain, striatum, and cerebral cortex. Furthermore, lithium treatment restored the activity of catechol-O-methyl transferase (EC 2.1.1.6) in young hyperthyroid rats to virtually normal limits. Our data suggest that antiphasic or damping effects of lithium upon mood swings is controlled, at least in part, by catecholaminergic systems in the brain. The interrelationship between brain catecholamines and thyroid hormones seems to be important to our understanding of the action of lithium in affective illness.

Animals↗
PubMed1977

Studies of neurotransmitter release in the pathogenesis of hypertension.

Studies using a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nervous system in essential hypertension. Methodology which allows the study of local sympathetic turnover in CNS nuclei and peripheral blood vessels is described. This approach has been used to study the non-innervated sympathetic turnover phaeochromocytoma. It is suggested that studies of local regulatory mechanism in neurotransmitter release are required to give a greater understanding of the central and peripheral role of the sympathetic nervous system in the pathogenesis of hypertension.

Adrenal Gland Neoplasms↗
PubMed1977

Organ culture of rat superior cervical ganglia.

The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine.

Animals↗
PubMedDate not supplied

Relationship between neurotransmitters and atherosclerosis.

Dyslipemia and finally the producing of atherosclerosis signal some modulation disturbances in neurotransmitters by the onset of a permanent incapacity of the organism to coordinate the adapting mechanism against the over-high activity of stress factors. Neurotransmitters and related substances facilitate and modulate energy and information in biosystems, assigning an important role to central control as noradrenaline, serotonin and other biogenic amines mediate emotional stress.

Arteriosclerosis↗
PubMed1977

Recent developments in the clinical assessment of the metabolism of aromatics by high-performance, reversed-phase chromatography with amperometric detection.

High-performance liquid chromatography with electrochemical detection has developed into a tool with excellent capability to monitor picomole amounts of individual metabolites in both tissue and body-fluid specimens. Significant technical advances in the area of microparticle chemically-bonded stationary phases have led to dramatic improvements in both sensitivity and resolution. Reversed-phase systems can be modified to include charged exchange sites by addition of detergents to the mobile phase. Adjustment of the surface charge in this manner permits capacity factors for ionic sample components to be increased or decreased. This concept is quite compatible with electrochemical detection and has provided the foundation for several clinical assays now in routine use. Examples of additional applications are presented for the determination of catecholamines in tissue, 3-methoxy-4-hydroxyphenylglycol in urine, and dopamine-beta-hydroxylase activity in human serum.

Animals↗
PubMed1977

Levels of neurotransmitters in brain of vitamin B12 deficient rats.

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.

Acetylcholinesterase↗