Density Of Uptake Sites Research Articles

MDMA-induced neurotoxicity: Parameters of degeneration and recovery of brain serotonin neurons

This study investigates a number of parameters that influence the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons in brain. Both the dose and number of injections of MDMA affect the degree of neurotoxicity on 5-HT axons and terminals as assessed by decreases in the content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the density of 5-HT uptake sites. Repeated systemic administration of various doses of MDMA (5–20 mg/kg twice daily for 4 consecutive days) results in dose-dependent decreases in 5-HT, 5-HIAA and 5-HT uptake sites. Increasing the number of injections of MDMA resulted in progressively greater reductions in 5-HT and 5-HIAA which occurred prior to decreases in 5-HT uptake sites. In contrast, no significant changes were observed in the density of norepinephrine uptake sites following single or repeated injections of 20 mg/kg MDMA. With respect to neuronal regeneration, following an initial 90% loss of 5-HT uptake sites after treatment with MDMA, the recovery of these sites occurred over a protracted period of time; a marked 25% reduction was seen at 6 months and the concentration of 5-HT uptake sites returned to control levels at 12 months following treatment with MDMA. Pretreatment with the selective 5-HT uptake blocker, citalopram, prior to each injection of MDMA prevented the neurotoxic effects of MDMA on the 5-HT parameters described above suggesting that active uptake of MDMA or a MDMA-related substance into brain 5-HT neurons was involved in the neurotoxic actions of the drug. In addition, the neurodegenerative effects of MDMA on 5-HT neurons exhibited some species specificity as comparable decreases in cerebral cortical 5-HT, 5-HIAA and 5-HT uptake sites were observed in rat and guinea pig while no significant changes in any of these serotonergic parameters were seen in mouse brain.

Decreased density of human striatal dopamine uptake sites with age

Decreased density of human striatal dopamine uptake sites with age

In vivo voltammetric characterization of low affinity striatal dopamine uptake: Drug inhibition profile and relation to dopaminergic innervation density

Electrical stimulation of the median forebrain bundle evoked dopamine release in the ipsilateral striatum which was monitored with high-speed cyclic voltammetry. After stimulation, the extracellular concentration of dopamine fell due to uptake in a biphasic manner, showing zero-order and first-order components. The zero-order phase corresponded to a V max of 42.8 ± 1.8nmol/min/g tissue. The uptake system could be blocked by d-amphetamine, methylphenidate and nomifensine, but not by benztropine, amfonelic acid or mazindol. The density of uptake sites showed a correlation with the density of striatal dopamine innervation.

Autoradiographic localization of adenosine uptake sites in rat brain using [3H]nitrobenzylthioinosine

The adenosine uptake site has been localized in rat brain by an in vitro light microscopic autoradiographic method, using [3H]nitrobenzylthioinosine ( [3H]NBI) as the probe. The binding characteristics of [3H]NBI on slide-mounted sections are comparable to those seen in studies performed on brain homogenates. A very high density of uptake sites occurs in the nucleus tractus solitarius, in the superficial layer of the superior colliculus, in several thalamic nuclei, and also in geniculate body nuclei. A high density of sites are also observed in the nucleus accumbens, the caudate putamen, the dorsal tegmentum area, the substantia nigra, and the central gray. The localization of the adenosine uptake site in brain may provide information on the functional activity of the site and suggests the involvement of the adenosine system in the central regulation of cardiovascular function.

Uptake of d-aspartate and l-glutamate in excitatory axon terminals in hippocampus: Autoradiographic and biochemical comparison with γ-aminobutyrate and other amino acids in normal rats and in rats with lesions

High affinity uptake sites for 3H-labelled amino acids were studied in synaptosome-containing homogenates processed biochemically or in surface autoradiograms of incubated slices of hippocampus. d-aspartate and l-glutamate had apparently identical distributions. In normal rat hippocampus the highest uptake was in the terminal fields of axons from the pyramidal cells of regio inferior and hilus fasciae dentatae, while there was a moderate uptake in the terminal fields of the medial and lateral perforant paths, slight uptake in the mossy fibre layer and no uptake in the terminal fields of the basket cells. Uptake sites for γ-aminobutyrate were concentrated in the latter fields, and in the most superficial cortical layers. The present method shows no uptake in cell bodies. The uptake activities were strongly inhibited by recognized blockers of (neuronal) high affinity uptake of glutamate or γ-aminobutyrate. Autoradiographically, several other amino acids showed negligible uptake. The uptake of d-aspartate was reduced by 80% in stratum oriens and stratum radiatum of regio superior 4–14 days (70% at 3 days) after transection of the afferent pyramidal cell axons from the ipsiand contralateral regio inferior. The reduction was in the number of uptake sites, not in their affinity. Uptake of γ-aminobutyrate was not reduced. Lesions affecting regio superior caused a loss of d-aspartate uptake in subiculum at a site known to receive hippocampal afferents. Autoradiographically, the uptake of d-aspartate was strongly reduced in the inner zone (i.e. the target zone), but increased in the middle zone of the dentate molecular layer after lesions of the hilus fasciae dentatae. At 4 days and longer after transection of the entorhinal afferents, there was a conspicuous reduction of d-aspartate and l-glutamate uptake in the target zones of both the medial and lateral contingent of these fibres. In the same animals, the terminal zone of afferents from hilus fasciae dentatae had an increased radioactivity and was slightly wider than normally. Concomitantly, the γ-aminobutyrate uptake was increased in the target zones of the degenerating perforant path fibres. The results demonstrate that uptake sites for d-aspartate and l-glutamate are highly localized in axon terminals of regio inferior pyramidal cells and in perforant path afferents. The latter category of terminals has a lower density of acidic amino acid uptake sites than the former. Uptake sites for γ-aminobutyrate are localized in terminals of intrinsic neurones, including the axosomatic terminals of basket cells. Lesion of one pathway induces reactive increase in the uptake sites in other pathways. The anatomy of the uptake sites matches the known anatomy of the fibre connections, normally and after denervation.

Biochemical indices of neuronal development in experimental phenylketonuria: high affinity transport systems and gangliosides.

High affinity transport systems and gangliosides were assessed in an animal model of experimental phenylketonuria, namely the rat injected with phenylacetate during the first 21 days of life. The velocity of synaptosomal high affinity uptake of [3H]-choline, [14C]-gamma-aminobutyric acid (GABA), and [14C]-glutamic acid served as a measure of the relative density of uptake sites of these specific types of terminals. A reduction of cholinergic (25-37%) and GABAergic (23-45%) functioning terminals was produced by phenylacetate in the hippocampal, occipital, and frontal cortices from 40- to 55- and 80- to 95-day-old rats. In contrast, glutamatergic terminals in these same areas of the cerebrum from animals of both ages were not affected. This selection effect of phenylacetate on synaptic junctions is discussed. Cerebral ganglioside content was reduced approximately 40% in experimental hyperphenylalaninemia induced with p-chlorophenylalanine and L-phenylalanine. A similar decrease was observed in the rat exposed to phenylacetate but not in the animal injected with phenylpyruvate. Short-term exposure to phenylacetate did not alter the capacity of the very young rat to utilize glucosamine for the biosynthesis and incorporation of sialic acid into gangliosides. The large decrease in cerebral ganglioside concentration and the significantly smaller percentage distribution of GM1, observed in the 19-day-old chronically exposed to phenylacetate, are apparently associated with deficient neuronal development.

The kinetics of ammonium and nitrate uptake by young rice plants

An important process which affects the fate of fertilizer nitrogen (N) applied to a rice crop is crop N uptake. This uptake rate is controlled by many factors including the N-ion species and its concentration. In this study the relation between N concentration at the root surface and N uptake was characterized using Michaelis-Menten kinetics. The equation considers two parameters, Vmax and Km, which are measures of the maximum rate of uptake and the affinity of the uptake sites for the nutrient, respectively. Uptake rates of intact rice plants growing in a continuously flowing nutrient solution system were fitted to the Michaelis-Menten model using a weighted regression analysis. For NH4−N the Km values for 4- and 9-week-old rice plants indicated a high affinity for the ammonium ions relative to concentrations reported for rice soils after fertilization. The Vmax values expressed on a unit-root-mass basis decreased with plant age, indicating a reduction in the average density of uptake sites on the root surface. The kinetics of NO3−N uptake was similar to that of NH4−N when NO3−N was the only N source. However, if NH4−N and NO3−N were present simultaneously in the solution the Vmax for the uptake of NO3−N was severely reduced, while the Km was affected very little. This inhibition appears to be noncompetitive. Fertilization of young rice plants leading to concentration of N at the root surface above approximately 900 μM will not increase crop uptake and may contribute to inefficient N recovery by the crop. The existence of NH4−N and NO3−N simultaneously at the root surface may also lead to inefficient N recovery because of reduced uptake of NO3−N.