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Biomedical subjects

M E Reith

Publications and source records attributed to M E Reith.

At least 127 records · Page 7Linked to original sources
PubMed1986

Structural requirements for cocaine congeners to interact with [3H]batrachotoxinin A 20-alpha-benzoate binding sites on sodium channels in mouse brain synaptosomes.

The present study examines the possible role of sodium channels in the behavioral effects of cocaine. Cocaine congeners are apparent competitive inhibitors of the scorpion toxin-enhanced binding of [3H]batrachotoxinin A 20-alpha-benzoate to sodium channels in mouse cerebrocortical synaptosomes. However, in agreement with the allosteric model for heterotropic cooperative interactions, the compounds produce a concentration-dependent increase in the rate of dissociation of binding. Concentrations that give a 2-fold increase of k-1 are close to Ki values for inhibiting equilibrium binding of [3H]bactrachotoxinin A 20-alpha-benzoate, suggesting that the inhibitory effect on binding results mostly from an increase of the apparent dissociation rate constant. The ester linkage between the tropane and benzoyl ring of cocaine is not essential for the inhibitory potency, and for both the C-2 and C-3 substituents the equatorial position results in a higher potency than the axial position. There is reasonable agreement between the rank order of potencies in blocking the sodium channel and in inhibiting locomotor behavior. The present results do not support a relationship between the capability of cocaine congeners in blocking sodium flux and in inhibiting uptake of dopamine into striatal synaptosomes. However, peak levels of cocaine in the brain of cocaine addicts could be high enough to interfere with sodium channel functioning, possibly contributing to some of cocaine's actions.

Allosteric Regulation↗
PubMed1986

Structural requirements for cocaine congeners to interact with dopamine and serotonin uptake sites in mouse brain and to induce stereotyped behavior.

We report here saturation analysis of [3H]cocaine binding in various mouse brain regions, and the necessary structure-activity relationships for cocaine congeners to inhibit Na+-dependent [3H]cocaine binding and [3H]dopamine uptake in the mouse striatum, and to inhibit [3H]cocaine binding that cannot be stimulated by Na+ and [3H]serotonin uptake in the mouse cerebral cortex. Generally similar structure-activity relationships were noted for all these processes. The ester linkage between the tropane and phenyl rings was not required for activity, in contrast to the configuration of the groups on C2, and to a lesser extent C3, in the tropane ring. Stereospecificity was evident from the differences between cocaine and (+)-pseudococaine, and between WIN 35,065-2 and WIN 35,065-3. There were remarkable differences between the above structure-activity relationships and those for local anesthetic activity of cocaine congeners, indicating that sodium channels were not labeled to a measurable extent with [3H]cocaine under the present conditions. Preliminary data indicated a significant correlation between the potencies of cocaine congeners in inhibiting the Na+-dependent binding of [3H]cocaine and their potencies in inducing stereotyped sniffing upon intraventricular administration.

Animals↗
PubMed1986

Effect of amphetamine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice.

Amphetamine has been shown to either potentiate or protect against MPTP neurotoxicity. The time course of changes in dopamine and its metabolites was examined after MPTP, amphetamine, or MPTP plus amphetamine administration. Results suggest that under conditions of granular depletion and release of dopamine by 10 mg/kg amphetamine, increased MPTP neurotoxicity occurs. Amphetamine injections at 2-5 mg/kg prevents the decline in dopamine possibly by blockade of the uptake of MPP+, rather than by an inhibition of monoamine oxidase.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Effect of nicotine and amphetamine on the neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

The present results show the potentiating effect of amphetamine on the ability of MPTP to destroy dopaminergic neurons in striatum of the mouse. A single injection of MPTP (8 mg/kg, retro-orbital) reduced the binding of [3H]mazindol, a marker for dopamine terminals, by 24%. When D-amphetamine (10 mg/kg, s.c.) was given 20 min prior to MPTP, the binding of [3H]mazindol, measured 3-5 days later, was reduced by 58%. It is proposed that the mechanism of this potentiation primarily involves an increased release of dopamine by D-amphetamine, and free radical-mediated processes. Although nicotine also releases dopamine from the striatum, no effect was observed when it was administered prior to MPTP. The lack of effect is probably related to short duration of action of nicotine and the modest effect on release of dopamine as compared to that of amphetamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Locomotor depression in mice by norcocaine does not involve central alpha 2-adrenergic or presynaptic dopamine receptors.

The inhibition of spontaneous locomotor behavior of mice by norcocaine was antagonized neither by the adrenoceptor antagonists yohimbine and phentolamine, nor by the neuroleptics haloperidol and spiperone, at low doses aimed at presynaptic dopamine receptors. In contrast, the antagonists were effective in reducing the hypomotility induced by clonidine and apomorphine, respectively. These results make it unlikely that central alpha 2-adrenergic or presynaptic dopamine receptors are involved in the hypomotive effect of norcocaine.

Animals↗
PubMed1986

Binding sites for [3H]cocaine in mouse striatum and cerebral cortex have different dissociation kinetics.

[3H]Cocaine dissociates from its binding sites in the mouse cerebral cortex with a half-time of 25 s. The dissociation kinetics in the striatum is consonant with the presence of two populations of sites with dissociation half times of 2 s and 27 s, comprising 88% and 12%, respectively, of the total binding sites. On the basis of previous pharmacological characterization of [3H]cocaine binding, we propose that the slowly dissociating component represents the sites associated with 5-hydroxytryptamine (serotonin) uptake, and the rapidly dissociating component the 3,4-dihydroxyphenylethylamine (dopamine)-related sites. Evidence is presented that the extremely high dissociation rates do not preclude the measurement of [3H]cocaine binding by rapid filtration. The dissociation of [3H]cocaine from cerebrocortical membranes is slowed to a small but statistically significant extent by serotonin.

Animals↗
PubMed1986

Binding of [3H]imipramine to mouse cerebrocortical membranes and to glass fiber filters.

It was suggested in a recent report by Phillips et al. [J. Neurochem. 43, 479-486 (1984)] that the low-affinity binding of [3H]imipramine in the mouse cerebral cortex could in fact represent binding of [3H]imipramine to the GF/B glass fiber filters used to terminate the assays. The present study demonstrates that this is not the case and advances two lines of evidence: (a) For saturation analysis, mouse cerebrocortical membranes were incubated with [3H]imipramine concentrations between 0.8 nM and 3.6 microM, and parallel incubations were carried out with buffer replacing the brain membranes. The same low-affinity component, in addition to the high-affinity component, was present in the binding of [3H]imipramine to brain membranes plus GF/B filters (uncorrected data), and in that to brain membranes alone (corrected data). (b) Dissociation experiments, in which filter binding is equal for all samples and dissociation time is the only variable, clearly indicated the nonhomogeneity of [3H]imipramine binding. Our results, however, do show that binding to recently purchased GF/B filters is not a negligible phenomenon in saturation experiments. Relatively lower binding was found to GF/C, GF/F, Gelman A/E, and Reeves Angel 934 AH filters; pretreatment of GF/B filters with polyethyleneimine (PEI) reduced binding to a greater extent in the single manifold than in the cell harvester.

Animals↗
PubMed1986

Isolation and nucleotide sequence analysis of the ferredoxin I gene from the cyanobacterium Anacystis nidulans R2.

Two mixed oligonucleotide probes derived from conserved regions of the Synechocystis sp. strain PCC 6714 ferredoxin amino acid sequence were utilized to isolate an Anacystis nidulans R2 clone containing the ferredoxin I gene. Nucleotide sequence analysis revealed a 297-base-pair (bp) open reading frame with a deduced amino acid sequence having high homology to other cyanobacterial ferredoxins. Assuming proteolytic cleavage of the initial methionine residue, the molecular weight of the mature A. nidulans R2 ferredoxin was 10,370. The initial methionine residue was preceded by a probable ribosome-binding site sequence, AGGA. Northern hybridization analysis with the cloned ferredoxin gene indicated an RNA transcript of approximately 450 bp. S1 nuclease mapping localized the transcription start site to a position 64 bases upstream from the initial methionine residue. The nucleotide sequence 14 to 8 bp preceding the transcription start site resembled a typical Escherichia coli promoter, but the sequence in the -35 region did not. Southern hybridization detected only a single copy of the ferredoxin sequence in the A. nidulans R2 genome.

Amino Acid Sequence↗
PubMed1985

Sodium-independent binding of [3H]cocaine in mouse striatum is serotonin related.

There was a highly significant correlation between IC50 values of various drugs in inhibiting the Na+-independent [3H]cocaine binding in the mouse striatum and their values in inhibiting the synaptosomal uptake of [3H]serotonin. In contrast, there was no correlation between the inhibition of binding in the absence of Na+ and the inhibition of [3H]dopamine uptake. Lesioning of serotonergic nerve terminals with 5,7-dihydroxytryptamine reduced the Na+-independent [3H]cocaine binding, without affecting the Na+-dependent binding. These results indicate that the bulk of the Na+-independent [3H]cocaine binding in the mouse striatum is associated with serotonergic nerve terminals.

5,7-Dihydroxytryptamine↗
PubMed1985

In vitro chloroplast protein synthesis by the chromophytic alga Olisthodiscus luteus.

The chloroplasts of chlorophytic and chromophytic plants exhibit significant morphological and biochemical differences. Presently, it is impossible to compare the influence of ctDNA on the structure and function of organelles within these two phylogenetic groups for no data exist in the literature on the profile of protein products synthesized by a chromophytic plastid. In this paper, the chloroplast DNA coded proteins of the chromophytic plant Olisthodiscus luteus are investigated by labeling isolated chloroplasts in vitro. Isolated plastids of excellent morphological condition are pulse labeled with [35S]methionine. Approximately 100 proteins are detected by two-dimensional gel electrophoresis and fluorography. However, these isolated plastids have a number of unusual characteristics: (1) they are photosynthetically inactive; (2) in vitro protein synthesis is light independent; (3) all proteins synthesized in vitro are membrane associated.

Chloroplasts↗
PubMed1985

In vivo chloroplast protein synthesis by the chromophytic alga Olisthodiscus luteus.

Information on the ctDNA protein coding profile of the Chlorophyta, Rhodophyta, and Chromophyta might provide clues to the evolutionary mechanism(s) by which plants diverged into these three phylogenetic groups. The purpose of this study was to examine the ctDNA protein coding profile of the chromophytic plant Olisthodiscus luteus. Whole cells were labeled in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Control experiments demonstrate that the chloroplast proteins labeled in vivo by this technique form a distinct subset of the total proteins synthesized by the cell. Approximately 50 plastid proteins (35 soluble, 15 membrane) were detected after two-dimensional gel electrophoresis and fluorography. Three ctDNA-coded proteins, the large subunit of ribulosebisphosphate carboxylase, the apoprotein of the P700-chlorophyll a-protein complex, and the "photogene" were identified. These proteins are also coded by chlorophytic ctDNA. Unexpectedly, the ctDNA of Olisthodiscus was shown to code for the small subunit of ribulosebisphosphate carboxylase. The gene for this enzyme subunit is nuclear coded in all chlorophytic plants that have been analyzed.

Chloramphenicol↗
PubMed1985

Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity by the antioxidant ascorbic acid.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 2 X 8 mg/kg retro-orbital) to BALB/cBy mice reduced [3H]mazindol binding to striatal membranes by 50%. Reactive oxygen derivatives have been suggested to be involved in MPTP neurotoxicity; therefore we examined the effects of ascorbic acid (an antioxidant). Ascorbic acid (100 mg/kg) given 20 min prior to MPTP administration appreciably prevented the reduction of [3H]mazindol binding. The involvement of oxidative processes in the mechanism of MPTP neurotoxicity may suggest a relationship to the etiology of Parkinson's disease, and the possible benefit of treatment with ascorbic acid.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Locomotor effects of cocaine, cocaine congeners, and local anesthetics in mice.

Spontaneous locomotor activity of mice was stimulated by IP administration of cocaine and its closely related phenyltropane analogs. In contrast, locomotion was inhibited by IP administration of cocaine congeners such as norcocaine, (+)-pseudococaine, and tropacocaine, and of isomers of phenyltropane analogs. Also inhibitory were the local anesthetics procaine, tetracaine, benzocaine, lidocaine, and prilocaine. The locomotor inhibition induced by IP norcocaine or tetracaine could be reversed by subsequent treatment with cocaine. Both cocaine and norcocaine were centrally stimulatory when injected intracerebroventricularly. The rank order of potencies of cocaine congeners and local anesthetics in depressing locomotion was similar to that of their potencies in interacting with sodium channels. From these results we infer that the locomotor depression induced by systemic administration of cocaine congeners results from a local anesthetic action involving inhibition of the ion conductance of sodium channels.

Anesthetics, Local↗
PubMed1985

Chloroplast Protein Synthesis in the Chromophytic Alga Olisthodiscus luteus: Cell Cycle Analysis.

This study represents the first report on chloroplast protein synthesis during the synchronous cell growth of a chromophytic (chlorophyll a,c) plant. When the unicellular alga Olisthodiscus luteus is maintained on a 12-hour light:12-hour dark cycle, cell and chloroplast number double every 24 hours. A temporal separation between these two events occurs. Measurements of chloroplast and total cellular protein values suggest that polypeptide synthesis occurs mainly in the light portion of the cell cycle, and pulse chase studies demonstrate that chloroplast proteins made in the light are not degraded in the dark. Data support the following conclusions: (a) a similar complement of chloroplast DNA coded proteins is made at all phases of the light portion of the cell cycle, and (b) chloroplast protein synthesis is a light rather than a cell cycle mediated response.

Journal Article↗
PubMed1985

Comparison of [3H]nicotine and [3H]acetylcholine binding in mouse brain: regional distribution.

In a continuing study of nicotine binding sites, we determined the relative amount of nicotine binding and acetylcholine binding in various brain regions of C57/BL and of DBA mice. Although midbrain showed the highest and cerebellum the lowest binding for both [3H]nicotine and [3H]acetylcholine, the ratio of nicotine to acetylcholine binding showed a three-fold regional variation. Acetylcholine inhibition of [3H]nicotine binding indicated that a portion of nicotine binding was not inhibited by acetylcholine. These results indicate important differences between the binding of (+/-)-[3H]nicotine and that of [3H]acetylcholine.

Acetylcholine↗
PubMed1984

Reduction of dopamine uptake and cocaine binding in mouse striatum by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) (daily injections of 8 mg/kg for 5 days via tail vein) reduced [3H]dopamine uptake in striatal synaptosomes by 63% and reduced [3H]cocaine binding to striatal membranes by 61%. [3H]Cocaine binding was not affected in olfactory tubercle, suggesting a selective effect of NMPTP on the nigro-striatal but not on the mesolimbic dopaminergic system. The destruction of dopamine terminals in the striatum did not alter (up-regulate) [3H]spiroperidol binding. The results suggest that NMPTP causes a degenerative destruction of the striatal dopamine pathway and that NMPTP may be useful in developing a rodent model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗