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E Meller

Publications and source records attributed to E Meller.

At least 73 records · Page 4Linked to original sources
PubMed1982

Differential dose- and time-dependent effects of molindone on dopamine neurons of rat brain: mediation by irreversible inhibition of monoamine oxidase.

The effects of molindone (2.5, 10 and 40 mg/kg) on striatal tyrosine hydroxylase activity and dopamine (DA), 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were measured as a function of time (0-72 hr). Whereas a dose of 2.5 mg/kg produced effects typical of DA receptor blockade (activation of synaptosomal tyrosine hydroxylase, increased DA metabolite levels and unchanged DA levels), a dose of 40 mg/kg produced opposite effects (decreased tyrosine hydroxylase activity and metabolite concentrations and elevated DA levels). A dose of 10 mg/kg elicited intermediate effects. The atypical effects of both higher doses were long-lasting (less than 72 hr). Molindone at doses of 10 or 40 mg/kg, but nor 2.5 mg/kg, selectively, irreversibly and dose-dependently inhibited type A monoamine oxidase. This inhibition appeared to be due to a metabolite, inasmuch as the drug itself inhibited monoamine oxidase (reversibly) only at high concentrations (less than or equal to 10(-4) M). The heretofore unsuspected inhibition of monoamine oxidase by molindone provided a consistent mechanistic interpretation of the differential dose- and time-dependent effects of the drug on dopaminergic neuronal activity. This mechanism may also serve to explain the reported efficacy of molindone in animal tests for antidepressant activity as well as its inability to produce increased DA receptor binding after chronic treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Chronic haloperidol does not increase specific dopamine receptor binding in rat frontal cortex.

The specific D2 dopamine receptor antagonist sulpiride was used to quantitate the minor component of [3H]spiroperidol binding (at 0.1 nM) to dopamine receptors in rat frontal cortex. Chronic treatment of rats with haloperidol, 0.5 mg/kg for 3 weeks or 2.5 mg/kg for 5 weeks, did not alter the specific binding of [3H]spiroperidol to dopamine receptors in frontal cortex, whereas both treatments significantly increased binding to striatal dopamine receptors. These findings may be relevant to previous studies demonstrating that the frontal cortex, but not the striatum, is resistant to the development of tolerance to the dopamine metabolite-elevating effects of chronic neuroleptic treatment.

Animals↗
PubMed1981

Lithium dissociates haloperidol-induced behavioral supersensitivity from reduced dopac increase in rat striatum.

Chronic lithium administration prevents both haloperidol-induced dopaminergic behavioral supersensitivity and increased tritiated neuroleptic binding to dopamine (DA) receptors in rat corpus striatum. Since chronic haloperidol treatment also induces tolerance to the activating effects to the drug on striatal DA synthesis, the ability of lithium to block neurochemical tolerance development was investigated. Whereas lithium treatment significantly (P less than 0.01) attenuated haloperidol-induced behavioral supersensitivity to apomorphine (0.33 and 0.66 mg/kg s.c.), it did not prevent tolerance to the elevation of striatal 3, 4-dihydroxyphenylacetic acid (DOPAC) levels 1 h after last treatment or in response to challenge with a low dose (0.1 mg/kg) of haloperidol during withdrawal. These results demonstrate a dissociation between the development of behavioral supersensitivity and the reduction in DOPAC increase. An assessment of lithium's demonstrated effects on supersensitivity development at various DA receptor sites suggests that tolerance may be mediated by presynaptic DA receptors on terminals of nigrostriatal neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

The effects of levulinic Acid and 4,6-dioxoheptanoic Acid on the metabolism of etiolated and greening barley leaves.

Application of levulinic acid (LA), a competitive inhibitor of delta-aminolevulinic acid (ALA) dehydratase, to greening plant tissues causes ALA to accumulate at the expense of chlorophyll. 4,6-Dioxoheptanoic acid (DA), which has been reported to be an effective inhibitor of this enzyme in animal systems, has a similar but more powerful effect on ALA and chlorophyll metabolism in greening leaves of Hordeum vulgare L. var. Larker. Both LA and DA also inhibit the uptake of [(14)C]amino acids into etiolated and greening barley leaves and reduce their incorporation into protein. Treatment of etiolated and greening leaves with these compounds results in the inhibition of (14)CO(2) evolution from labeled precursors, including amino and organic acids. Inhibition of (14)CO(2) evolution by these compounds is more effective in greening leaves than in etiolated leaves when [4-(14)C]ALA or [1-(14)C]glutamate are employed as precursors. Both LA and DA also inhibit the uptake and increase the incorporation of (32)Pi into organophosphorus by etiolated barley leaves. These results indicate that LA and DA have more far-reaching effects upon plant metabolism than was previously believed.

Journal Article↗
PubMed1981

Studies with 4,6-dioxoheptanoic Acid on etiolated and greening barley leaves.

4,6-Dioxoheptanoic acid (DA), an inhibitor of 5-aminolevulinic acid (ALA) dehydratase (EC 4.3.1.24), causes ALA to accumulate at the expense of chlorophyll when applied to greening leaves of Hordeum vulgare L. var. Larker. Preincubating etiolated leaves with DA in darkness eliminates the lag phase in ALA accumulation during a subsequent exposure to illumination. More than 50% of the DA taken up during a 2-hour incubation disappeared during a subsequent 4-hour incubation. These results suggest that barley leaves can metabolize DA, and the products of this metabolism may enhance the capacity for ALA synthesis.

Journal Article↗
PubMed1981

Catabolism of [1-C]levulinic Acid by etiolated and greening barley leaves.

Levulinic acid (LA), a competitive inhibitor of delta-aminolevulinic acid (ALA) dehydratase (EC 4.2.1.24), has been used extensively in the study of ALA formation during greening. When [1-(14)C]LA is administered to etiolated barley (Hordeum vulgare L. var. Larker) shoots in darkness, (14)CO(2) is evolved. This process is accelerated when such tissues are incubated with 2 millimolar ALA or placed under continuous illumination. Label from the C-1 of LA becomes incorporated into organic acids, amino acids, sugars, lipids, and proteins during a 4-hour incubation in darkness or in the light. This metabolism is discussed in relation to the use of LA as a tool in the study of chlorophyll synthesis in higher plants.

Journal Article↗
PubMed1981

Effects of conformationally restrained analogues of serotonin on its uptake and binding in rat brain.

Two series of serotonin analogues, in which the side chain amino group is constrained in the gauche or trans conformation, were utilized to study the preferred conformation of serotonin for interaction with two different neuronal sites. 6-Hydroxytetrahydro-beta-carboline and 6-hydroxy-3-aminotetrahydrocarbazole were found to be potent inhibitors of serotonin uptake into hypothalamic synaptosomes, with IC50 values of 0.13 microM for each analogue. The type of inhibition, as determined by Dixon plots, was found to be competitive, with Ki's of 3.0 X 10(-8) M and 4.6 X 10(-8) M for the beta-carboline and carbazole derivatives, respectively. Methoxylation or lack of a hydroxy group at the 6 position of the carbazole derivative did not alter inhibitory potency, while methoxy or benzyloxy substitution decreased potency 22- to 326-fold. The serotonin analogues were 20 to 30 times less potent in inhibiting the synaptosomal transport of the catecholamines. With regard to [3H]serotonin binding to membranes obtained from brain homogenates, both analogues exhibited poor affinity compared with the transmitter. However, the beta-carboline derivative was three times as potent as the carbazole analogue. These findings and earlier ones with regard to the effect of the serotonin analogues on brain monoamine oxidase activity support the idea that serotonin analogues interact differentially with the three different serotonergic sites examined.

Animals↗
PubMed1978

Pharmacological and biochemical properties of isomeric yohimbine alkaloids.

The stereochemical and pharmacological properties of yohimbine and some of its isomers are briefly reviewed. Several pharmacological and physical properties of a selection of the isomers have been determined with a view to elucidating which might be important in the elaboration of the known behavioral effects produced by them. Activity is not dependent upon lipid solubility or on the ease of access to the central nervous system. The isomers are weak inhibitors of rat-brain acetylcholinesterase and weak antagonists at muscarinic cholinergic receptors. In the rat brain in vitro they do not possess significant monoamine oxidase-inhibiting properties nor do they inhibit the uptake of serotonin. They are relatively potent antagonists of 5HT on the rat isolated fundus preparation and their potency in this preparation may be related to their ability to produce behavioral and cardiovascular effects in man and dogs.

Animals↗
PubMed1975

5-methyltetrahydrofolic acid is not a methyl donor for biogenic amines: enzymatic formation of formaldehyde.

Contrary to previous reports, 5-methyltetrahydrofolic acid does not mediate the methylation of dopamine to epinine. Instead, this methyl donor is degraded enzymatically to formaldehyde, which condenses with dopamine to form a tetahydoisoquinoline derivative. The latter has chromotographic characteristics very similar to those of epinine, which likely accounts for the original misidentification of the product.

Animals↗
PubMed1975

Accumulation of delta-Aminolevulinic Acid and Its Relation to Chlorophyll Synthesis and Development of Plastid Structure in Greening Leaves.

Levulinic acid inhibited the greening of etiolated maize (Zea mays) and bean (Phaseolus vulgaris) leaves and caused accumulation of delta-aminolevulinic acid (ALA). ALA accumulation in maize was equivalent to the decrease in chlorophyll, over a wide range of experimental conditions. It was saturated at low light intensities and was not limited by the supply of substrates during the early hours of greening. During 20 hours in light, levulinic acid had little effect on the structural development of thylakoids in bundle sheath chloroplasts but significantly reduced the number and size of thylakoids in grana of mesophyll chloroplasts. Recrystallization of prolamellar bodies and their reformation was inhibited. Mitochondria appeared not to be affected.The accumulation of ALA in bean leaves differed from that in maize in regard to its time course and the effect of levulinic acid concentration and light intensity. The amount of ALA accumulated exceeded that expected from the degree of inhibition of chlorophyll synthesis. Levulinic acid caused abnormalities in the structural development of bean chloroplasts and marked swelling of mitochondria.Chloramphenicol and cycloheximide inhibited ALA accumulation, while inhibitors of RNA synthesis had no effect. The extent of inhibition depended on the time the inhibitor was applied during the greening process. The use of ALA accumulation as a tool for studying the control of chlorophyll synthesis is discussed.

Journal Article↗
PubMed1975

Control of delta-Aminolevulinic Acid and Chlorophyll Accumulation in Greening Maize Leaves upon Light-Dark Transitions.

The accumulation of delta-aminolevulinic acid (ALA) was studied in greening maize (Zea mays) leaves which were transferred to darkness and reilluminated after various periods of time. The system synthesizing ALA decays in the dark with a half-life of about 80 minutes. The onset of enzyme decay after transfer to darkness shows a 40-minute lag. The accumulation of ALA in the presence of levulinic acid in leaves transferred to darkness corresponds to that expected from the estimated half-life of the enzyme synthesizing ALA. On the other hand, the accumulation of protochlorophyll upon transfer to darkness in the absence of levulinic acid stops much earlier. It is suggested that a control point exists in the pathway between ALA and protochlorophyll, preventing utilization of the accumulated ALA upon transfer of greening leaves to darkness. This is supported by the observed effects of low intensities of monochromatic light (648 nm) on ALA and chlorophyll accumulation.

Journal Article↗