Monoamine Oxidase and Cerebral Uptake of Dopaminergic Drugs

Cotzias, George C.; Tang, Lei-Han; Ginos, James Z.

doi:10.1073/pnas.71.7.2715

Cited by 21 publications

(13 citation statements)

References 24 publications

(22 reference statements)

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“…The inhibition of monoamine oxidase (MAO) activity by MB has been known for many decades (Philpot, 1937; Philpot and Cantoni, 1941; Imaizumi et al, 1959; Ehringer et al, 1961; Cotzias et al, 1974). It was reported that MB (0.5 μM) potently inhibited the activity of MAO in guinea pig liver homogenates and potentiated the vasoconstriction induced by tyramine (Imaizumi et al, 1959).…”

Section: Methylene Blue and Neurotransmitter Systemsmentioning

confidence: 99%

Cellular and molecular actions of Methylene Blue in the nervous system

Öz

Lorke

Al‐Hasan

et al. 2010

Medicinal Research Reviews

349

249

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Methylene Blue (MB), following its introduction to biology in the 19 th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system.

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Section: Methylene Blue and Neurotransmitter Systemsmentioning

confidence: 99%

Cellular and molecular actions of Methylene Blue in the nervous system

Öz

Lorke

Al‐Hasan

et al. 2010

Medicinal Research Reviews

349

249

View full text Add to dashboard Cite

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“…The means and standard errors of the effects of apomorphine (Table 3), scored by a system different from that used for levodopa (30), were diminished by cycloheximide, chloramphenicol, and puromycin in intact mice. Caudectomized mice treated with the apomorphine (2 jsg/g, i.p.)…”

Section: Observationsmentioning

confidence: 99%

Changing the Actions of Neuroactive Drugs by Changing Brain Protein Synthesis

Tang¹,

Cotzias²,

Dunn³

1974

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

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Diminution of cerebral protein synthesis diminished the cerebral responses of mice to some neuroactive drugs, while an increase in synthesis increased the responses. Protein synthesis in whole brains (tested in vitro ) was diminished by giving living mice different inhibitors by different routes. The inhibitors tested (chloramphenicol, cycloheximide, and puromycin) diminished the behavioral responses of the mice to levodopa without affecting either its cerebral uptake or its conversion to dopamine. A diminution of the reactions of dopaminergic receptors was suggested by the diminished responses to the dopaminergic drug, apomorphine, while participation of cholinergic ones was suggested by experiments with oxotremorine. Proof that receptors had been specifically involved was secured on homogenized caudate nuclei from chloramphenicol-treated mice, in which the dopamine-activated production of cyclic AMP was markedly diminished. A stimulator of cerebral protein synthesis, the artificial double-stranded RNA, poly(I)·poly(C), increased the behavioral responses to these three drugs while it increased the dopamine-activated production of cyclic AMP. Since all these experimental increases or decreases in the responses to drugs required the lapse of only a few hours, proteins with rapid turnover rates must be critical in the activation of several kinds of cerebral receptors.

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“…The method of measuring adenylate cyclase activity has been described earlier (20). Various concentrations of morphine ranging from 1 ,uM to 5 mM in either 50 ,ul of solution or in 25 Al together with 25 ,l of 5 mM dopamine or 25 ,uM naloxone were added to the homogenates prior to the addition of ATP, which initiates the reaction.…”

Section: Methodsmentioning

confidence: 99%

“…Caudate nuclei of the mice were excised as for the adenylate cyclase determination and homogenized in 6 ml of 50 mM Tris-HCl, pH 7.5. Aliquots (1.9 ml) each of the homogenates were incubated for 5 min at 35°in triplicate with one of the following: 25 ,l of 0.1 ,uM morphine, 25 ,ul of 5 mM dopamine, 25 ,l of 0.1 ,uM morphine plus 5 ml of cold Tris-HCI. One milliliter of 10% sodium dodecyl sulfate was added to the dried filters, which were shaken in scintillation vials for 30 min.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Morphine sulfate stimulates the adenylate cyclase in mouse caudate nuclei.

Tang¹,

Cotzias²

1978

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

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The effect of several concentrations of morphine on the activity of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] was measured in homogenates of caudate nuclei of mice. Morphine stimulated the enzyme at 500 MM and inhibited slightly at 5 MM. Morphine stimulation was blocked by naloxone. Depending on its dose, morphine also increased or decreased the stimulating effect of dopamine on the dopamine-sensitive adenylate cyclase activity of caudate homogenate. Like dopamine, morphine's effect on the adenylate cyclase activity was increased or decreased, respectively, by retreating the animals with poly(I)poly(C) or with chlorampbenicol. Thus, both dopamine and morphine appear to act on the same receptor. This "new" receptor differs from the one described by Snyder et al. and others, who demonstrated only binding affinity and no enzymatic activity. These data indicate that certain functions of the opiates might be mediated through the dopamine-sensitive adenylate cyclase of the caudate nuclei, which are the dopamine receptors in the brain.Levodopa(L-dopa, L-3-4-dihydroxyphenylalanine) has been reported to relieve pain caused by bone metastases of breast cancer (1, 2) and other cancers (3). Recent microphysiological studies have shown that lamina V cells in the spinal dorsal horn take part in the integration and transmission of noxious stimuli to brain (4). Both levodopa and morphine inhibit the activities of the lamina V cells of the dorsal horn of the rabbit (5), and both are analgesic. We have found that feeding levodopa to mice promoted longevity (6, 7) and increased the dopaminesensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity without changing the basal cyclase activity in the caudate nuclei of these mice (8). When morphine pellets (75 mg of morphine base) were implanted subcutaneously in rats for 5 days, the dopamine-sensitive adenylate cyclase activity increased, but the basal cyclase remained steady (9).The above findings suggested to us that dopamine and morphine may act on the same receptors in the nervous system, particularly those in the caudate nuclei. We, therefore, investigated competition between morphine and dopamine on the dopamine-sensitive adenylate cyclase. We also tested the effect of these compounds on another enzyme important in dopamine metabolism, monoamine oxidase [amine:oxygen oxidoreductase (deaminating) (flavin-containing) MATERIALS AND METHODSAnimals. Swiss Albino Hale Stoner male mice, 5-7 weeks old, weighing 22-27 g, were housed six to a cage in an air-conditioned room with a light-to-darkness cycle of 12 hr. Purina laboratory chow and water were given ab libitum. Three hours before the effects of morphine and dopamine were measured, some animals were pretreated with either chloramphenicol (1.5 mg/g of body weight by gastric tube twice) or the doublestranded RNA poly(I)-poly(C) (1.5 ,Ag/g of body weight) which, respectively, decreased or increased the effects of levodopa both on behavior of intact animals and the dopami...

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Monoamine Oxidase and Cerebral Uptake of Dopaminergic Drugs

Cited by 21 publications

References 24 publications

Cellular and molecular actions of Methylene Blue in the nervous system

Cellular and molecular actions of Methylene Blue in the nervous system

Changing the Actions of Neuroactive Drugs by Changing Brain Protein Synthesis

Morphine sulfate stimulates the adenylate cyclase in mouse caudate nuclei.

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