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PubMed1985

The role of compartmentation and glycerol kinase in the synthesis of ATP within the glycosome of Trypanosoma brucei.

Glycosomes, purified from trypomastigote forms of Trypanosoma brucei, contained all the enzymes necessary to convert glucose to alpha-glycerophosphate and 3-phosphoglycerate. The multienzyme reaction which produces 2 alpha-glycerophosphate, 2 ADP, and 2 NAD+ from 1 glucose, 2 ATP, and 2 NADH was studied spectrophotometrically. Intact glycosomes, suspended with 5.6 mM alpha-glycerophosphate and 2 mM ADP, produced ATP inside the glycosomes for glucose phosphorylation at a rate of 0.7 mumol/min/mg protein, so confirming the feasibility of producing ATP from alpha-glycerophosphate and ADP catalyzed by glycosomal glycerol kinase, and coupling this ATP production to the ATP-requiring stages of glycolysis. No evidence was found for direct channeling of the ATP generated by glycerol kinase and either hexokinase or phosphofructose kinase in glycosomal enzyme complexes cross-linked by dimethyl suberimidate treatment of intact glycosomes prior to solubilization of their membrane. Compartmentation of glycolytic intermediates, enzymes, and ATP inside isolated glycosomes was demonstrated by their inaccessibility to exogenous enzymes. We conclude that the compartmentation of the glycosome and the efficient production of ATP in the glycosome from whole cell concentrations of sn-glycerol 3-phosphate and ADP account for the observed whole cell production of equimolar glycerol from glucose with net ATP synthesis by T. brucei under anaerobic conditions.

Adenosine Diphosphate↗
PubMed1988

Protein secretion and compartmentalization in yeast.

Genetic and biochemical techniques are being employed to study the transport and compartmentalization of proteins in Saccharomyces cerevisiae. A number of thermosensitive sec mutants have been isolated which are blocked at different stages of the secretory route (endoplasmic reticulum, Golgi complex, secretory vesicles, cell surface). They offer the possibility of analyzing protein processing along this pathway, by studying the molecular intermediates accumulated in the mutants at the nonpermissive temperature. Compartmentalization of the proteins is influenced by cellular functions, as well as by their own peptide sequence of the molecules to be targeted. The physical structure of the wall is also important for the incorporation of mannoproteins into it. Factors affecting expression and externalization of heterologous proteins in yeasts are also reviewed.

Biological Transport↗
PubMed1986

Functional compartmentation of intracellular magnesium.

Due to the distribution of Mg2+-binding ligands, such as DNA, RNA, or Mg2+-binding proteins, e.g. within the intermembranous space of mitochondria, intracellular magnesium is compartmentalized. Furthermore, cytosolic free Mg2+ is enriched at charged surfaces. Thus, the exact concentration of free intracellular Mg2+ can only be ascertained for a small volume element. Compartmentation of intracellular Mg2+ can also be determined by flux measurements with 28Mg2+. In different cell types, cellular Mg2+ is exchanged with different velocities, and, in some cell types, rapidly and slowly or non-exchangeable compartments are detectable. Cells can be Mg2+-depleted gradually by incubation with A23187 and EDTA. In cells which are Mg2+-depleted gradually, the Mg2+-dependent metabolic functions are inhibited in the following sequence: glycolysis, RNA, DNA synthesis, respiration, protein synthesis, protein synthesis appears to be the most sensitive function affected.

Animals↗
PubMed1995

Functional compartmentation of dCTP pools. Preferential utilization of salvaged deoxycytidine for DNA repair in human lymphoblasts.

The utilization of dCTP derived from de novo synthesis through ribonucleotide reductase in exponentially growing CCRF-CEM cells was compared with the metabolic fate of dCTP produced by the salvage pathway. Exogenous dCyd was not effectively incorporated into replicating DNA; instead, dCTP derived from ribonucleotide reductase (labeled by [5-3H]Cyd) was the main precursor for that purpose, apparently because of functional compartmentation of the dCTP pool in these cells. Studies of the metabolic route of incorporation of exogenous [5-3H]dCyd into DNA of growing CCRF-CEM cells demonstrated that it was mainly incorporated through the DNA repair pathway. Incorporation of [5-3H]dCyd into DNA of synchronized cell populations was maximal in G1 cells, whereas [3H]dThd incorporation occurred predominantly in S phase cells. When cellular DNA was density labeled by incubation with BrdUrd, repaired DNA, which was less dense than replicated DNA, was preferentially labeled by [5-3H]dCyd. In contrast, replicated DNA was labeled by both [3H]dThd and [5-3H]Cyd. The DNA-damaging agents methylmethanesulfonate, ultraviolet irradiation, and gamma-irradiation inhibited [3H]dThd incorporation, whereas they stimulated the accumulation of [5-3H]dCyd in DNA. Based on these results, we propose that the dCTP pool is functionally compartmentalized in growing CCRF-CEM cells. dCTP derived from the salvage pathway is utilized predominantly for DNA repair, whereas the de novo pathway supplies dCTP for DNA replication.

Bromodeoxyuridine↗
PubMed1998

Effect of catechol-O-methyltransferase inhibition on brain uptake of [18F]fluorodopa: implications for compartmental modelling and clinical usefulness.

The efficacy of levo-DOPA in the treatment of Parkinson's disease is potentiated by blockade of its peripheral metabolism with inhibitors of catechol-O-methyltransferase (COMT). Some COMT inhibitors may act entirely in the periphery (nitecapone, OR-462), while others may also have some activity in brain (entacapone, OR-611). We used positron emission tomography (PET) to test the effects of these two COMT inhibitors on the plasma kinetics and brain metabolism of the levo-DOPA analog 6-[18F]fluoro-L-dopa (FDOPA) in cynomolgus monkeys, employing a compartmental model for the assay of DOPA decarboxylase activity in living brain. Four monkeys each underwent two PET scans in the baseline condition, one PET scan after treatment with OR-462 (15 mg/kg, i.v.), and one PET scan after treatment with OR-611 (15 mg/kg, i.v.). Pharmacokinetic analysis of FDOPA metabolism in plasma indicated that these compounds blocked peripheral COMT activity by 80% for at least 60 minutes. Both COMT inhibitors increased the net availability of FDOPA in circulation, and increased the ratio of the radioactivity concentrations in striatum and occipital cortex, suggesting that [18F]fluorodopamine synthesis in striatum was potentiated. However, OR-611 treatment reduced the unidirectional (K1D) and net (Ki) blood-brain clearances of FDOPA, and also inhibited the rate of decarboxylation (k3D) of FDOPA in striatum. These observations suggest that high doses of OR-611 may partially antagonize the cerebral utilization of levo-DOPA. We used the present data to test the sensitivity of the compartmental model to the physiological constraint that the blood-brain permeabilities of the O-methylated plasma metabolite and FDOPA have a fixed ratio. In the groups with COMT inhibition, the estimates of k3D were insensitive to the magnitude of the permeability ratio. In the control group, the estimate of k3D increased by 40% as the magnitude of the constrained permeability ratio increased in the range of published estimates.

Animals↗
PubMed1999

Magnetic resonance imaging-based compartmentation and its application to measuring metabolite concentrations in the frontal lobe.

Partial volume mixing of water compartments within a spectroscopy voxel (e.g. cerebrospinal fluid within a "brain" voxel) may, if not corrected for, lead to underestimation of brain metabolite concentrations. To correct for this source of bias, a new imaging-based method of compartmentation analysis is presented. Brain water, cerebrospinal fluid and solid matter content were obtained from proton density- and T2-weighted images of the brain and an external standard in 10 healthy young males (21 to 30 years), and results compared with a previously-described technique based on spectroscopy. Mean (SD) fractional water content (betaMR) of the 2 x 2 x 2 cm3 voxel in the frontal lobes was 0.79 (0.03) by imaging, slightly but significantly (p = 0.03) smaller than the value of 0.83 (0.03) obtained by spectroscopy. From water-suppressed spectra recorded at five echo times, using betaMR determined by imaging, the T2-corrected concentrations of compounds containing N-acetylaspartate, creatine, choline and myo-inositol were 10.6 (1.0), 8.0 (0.9), 1.6 (0.3) and 3.7 (0.7) mmol.l(-1) of brain, respectively. Imaging-based compartmentation is a rapid and straightforward technique, and can be performed on standard MR systems.

Adult↗
PubMed1980

Motor-end-plate and nerve distribution in a histochemically compartmentalized pennate muscle in the cat.

Previous investigations in this laboratory have shown the flexor carpi radialis muscle (FCR) of the cat to be compartmentalized with regard to the distribution of muscle fiber types. This study was undertaken to determine whether each compartment of the FCR had a distinct motor innervation band, or whether there was only one innervation band, as has been reported previously for other muscles. In order to assess variation in motor innervation banding patterns, the innervation bands were correlated with the muscle-tendon architecture. Each compartment of the FCR possessed a distinct innervation band. In addition, it was observed that the nerve to the FCR divided into a number of separate intramuscular branches which were distributed to the different histological compartments. It is possible that muscle fibers innervated by a single intramuscular nerve branch, and possessing a discrete innervation band, are locally organized within subdivisions of the FCR. It is hypothesized that the compartmental organization of the FCR would allow discrete regions of the muscle to function independently when performing different motor tasks.

Animals↗
PubMed2006

Compartmentalization of oxidative stress and antioxidant defense in the larval gut of Spodoptera littoralis.

Allelochemicals play important roles in the plant defense against herbivorous insects. They act as feeding deterrents, interfere with digestion and nutrient absorption, and cause production of potentially dangerous oxidative radicals. This study demonstrates that the distributions of oxidative radicals and of the antioxidant enzymes that eliminate them are compartmentalized in the digestive tract of Spodoptera littoralis larvae. Feeding on diets supplemented with the tannic acid (TA), alpha-solanine, and demissidine, respectively, did not affect the rate of food passage through the digestive tract of larvae but 1.25, 2.5, and 5% TA evoked a strong oxidative response. The amount of the superoxide anion in the foregut tissue and content increased up to 70-fold and the titer of total peroxides in the foregut content about 3-fold. This oxidative stress was associated with enhanced carbonyl content in the foregut tissue proteins, indicative of certain tissue deterioration. Extensive foregut damage was probably prevented by elevated activity of the glutathione S-transferase peroxidase. A complex antioxidant response was elicited in the midgut. The activities of superoxide dismutase and catalase increased significantly in the midgut tissue and content, and the activity of ascorbate peroxidase rose in the midgut tissue. The enzymes apparently eliminated oxidative radicals passing to midgut from the foregut with the food bolus and thereby prevented carbonylation of the midgut proteins. We postulate that the generation of oxidative radicals in the foregut and the induction of antioxidant defense in the midgut are controlled processes and that their compartmentalization is an important functional feature of the digestive tract. The glycoalkaloid alpha-solanine and the aglycone demissidine applied at 0.05 and 0.1% concentrations had no effect on any of the examined parameters.

Animals↗
PubMed2003

Compartmentation of the mouse cerebellar cortex by neuronal calcium sensor-1.

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. The detailed distribution of NCS-1 was analyzed in the mouse cerebellar cortex. In coronal sections, the NCS-1 immunostaining displayed characteristic parasagittal banding pattern in the Purkinje cell layer and molecular layer, while there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate-basket cells were uniformly NCS-1-positive throughout the cerebellum. Immunofluorescent double staining showed that NCS-1 and zebrin II exhibited a similar parasagittal banding pattern. Then, we performed mapping of NCS-1- and/or zebrin II-labeled Purkinje cell somata using seven sequential coronal sections. NCS-1-positive/zebrin II-positive Purkinje cell clusters were seen throughout the cerebellum, but NCS-1-positive/zebrin II-negative Purkinje cells were exceedingly rare. On the other hand, NCS-1-negative/zebrin II-positive Purkinje cell clusters were found in anterior lobule vermis and paraflocculus, whereas they were rarely seen in posterior lobules. The digitized quantitative analysis showed close relationship between NCS-1 and zebrin II immunoreactivity in the molecular layer. The correspondence between NCS-1 and zebrin II demonstrated here indicates a novel anteroposterior difference of cerebellar compartmentation and provides fundamental information of cerebellar organization.

Animals↗
PubMed1986

Myeloarchitecture of the cerebellum of the chicken (Gallus domesticus): an atlas of the compartmental subdivision of the cerebellar white matter.

A myeloarchitectonic atlas of the longitudinal (or mediolateral) subdivision of the cerebellum of the chicken (white Leghorn) was prepared from serial Häggqvist or toluidine-blue-stained sections of five animals. This myeloarchitectonic subdivision is based on the alternate occurrence of large fiber accumulations (LFAs) and small fiber areas (SFAs) in the cerebellar white matter and allows the distinction of a number of parasagittal fiber compartments, each of which consists of a medial LFA and a lateral SFA. The compartmental subdivision of the cerebellar white matter in mammals and birds derives its importance from the fact that essentially it corresponds to the organization of the afferent and efferent connections of the cerebellar cortex. The simple structure of the avian cerebellum makes it ideally suited for a complete description of its compartmental subdivision and may serve as a natural system of coordinates in future anatomical and physiological studies. The number of fiber compartments that can be counted in the chicken cerebellum on either side of the midline varies from six (in the narrowest folium I) to nine (in the widest folia IX and X) and is approximately the same as in mammals, in which a maximum of eight or ten compartments can be recognized. On the basis of the organization of its myeloarchitecture and the otherwise relatively scarce data on the organization of the connections of its cortex, it can, therefore, be postulated that the avian cerebellum is the homologue of the entire mammalian cerebellum. In addition, the present knowledge of the connections of the cerebellar cortex in birds indicates that the avian compartments 1-3 may correspond to the mammalian compartments A1, A2, and A3 (or X), whereas the avian compartment 4 or 5 (or both) may represent the mammalian B compartment. Lack of further anatomical data so far precludes conclusions on a possible homology between the avian compartments 6-9 and the mammalian C and D compartments.

Animals↗
PubMed1988

Ventral striatopallidal parts of the basal ganglia in the rat: I. Neurochemical compartmentation as reflected by the distributions of neurotensin and substance P immunoreactivity.

The distribution of neurotensin immunoreactivity in the basal ganglia of the adult rat was evaluated by studying alternate serial vibratome sections that were exposed to antiserum against neurotensin, substance P, or cholecystokinin. It was observed that a heterogeneous distribution of neurotensin-immunoreactive fibers and terminals contributes to the neurochemical compartmentation of the ventral pallidum and ventral striatum, and that significant numbers of neurotensin-immunoreactive neurons occupy striatal districts of the olfactory tubercle, nucleus accumbens, and ventromedial caudate-putamen. An intense band of pallidal neurotensin immunoreactivity characterizes the medial part of the ventral pallidum adjacent to the nucleus accumbens, whose medial boundary is conveniently defined in sections incubated with cholecystokinin antiserum. Electron microscopic studies showed that the pallidal plexus of neurotensin-immunoreactive elements consists primarily of boutons, which contact large dendrites in arrangements that in all respects appear to be of the classical striatopallidal variety. A gradual decrease in immunolabel was observed approaching the lateral parts of the ventral pallidum, which display sparse neurotensin immunoreactivity. The results thus indicate the existence of a significant neurotensinergic striatopallidal pathway confined primarily, if not exclusively, to the medial part of the ventral striatopallidal system. The contribution of neurotensin-immunoreactive fibers and terminals to the compartmentation of ventral striatum is expressed most vividly in their exclusion from clusters of tightly packed medium-sized neurons, many of which are intensely substance P immunoreactive. Such clusters appear identical with those previously described as rich in opiate receptors and poor in acetylcholinesterase activity. In the ventral striatal region where the nucleus accumbens and ventromedial caudate-putamen merge, neurotensin-immunoreactive neurons are organized in clusters. Further rostral in the nucleus accumbens, they are more evenly distributed. Few were found in the dorsolateral quadrant of the neostriatum.

Animals↗
PubMed1990

Compartmental and topographical specificity of reinnervation of the glutaeus muscle in the adult toad (Bufo marinus).

The extent to which the compartmental and topographical innervation patterns were re-established in the mature glutaeus muscle after nerve cut was determined by HRP retrograde labelling procedures and single motor unit glycogen depletion experiments. Glutaeus muscle axons normally cluster together along the length of the sciatic nerve and enter the triceps femoris nerve along with axons to the cruralis and tensor fasciae latae muscles. Glutaeus axons did not specifically reinnervate the glutaeus muscle after cutting the triceps femoris nerve. Axons within the glutaeus muscle nerve are grouped according to the primary nerve branch, and therefore muscle compartment, for which they are destined. When the glutaeus nerve was cut, regenerating axons lost their compartmental organization within the glutaeus nerve and nonspecifically reinnervated both glutaeus muscle compartments. In marked contrast, the topographical projection of spinal motoneurones to the ventral and dorsal halves of the glutaeus muscle was largely re-established after glutaeus nerve cut; that is, rostral motoneurones mostly reinnervated ventral muscle fibres, whereas caudal motoneurones reinnervated dorsally located muscle fibres. The relatively confined caudal projection was closely related to the sharp fibre type divisions within the glutaeus muscle. The results suggest that factor(s) present during development that determine the correct innervation of a muscle and its compartments no longer operate in the adult, although cues that direct motor terminals to their appropriate muscle region do, and these are most likely related to the topographical distribution of fibre types.

Animals↗
PubMed1991

Compartmental organization of the thalamostriatal connection in the cat.

The compartmental organization of the thalamostriatal connection in the cat was studied by labelling thalamic fibers in anterograde axonal transport experiments and comparing their striatal distributions with the arrangement of striosomes and matrix tissue identified by histochemical staining methods. When analyzed according to their principal compartmental targets in dorsal striatum, the thalamic deposits indicated the existence of medial and lateral divisions within the thalamostriatal projection. Nuclei of the medial division, which includes parts of the thalamic midline, projected primarily to striosomes. The lateral division, which embraces the anterior and posterior intralaminar groups, the rostral ventral tier nuclei, and parts of the posterior lateral nuclear complex, predominantly innervated matrix tissue. In the dorsal division of the nucleus accumbens, the medial system preferentially terminated in zones that stain heavily in butyrylcholinesterase and substance P preparations, but fibers from both the medial and the lateral systems largely avoided the histochemically marked compartments such as the border islands of the nucleus accumbens that are seen elsewhere in the ventral striatum. Medial division: Thalamic deposits involving the paraventricular and rhomboid nuclei of the thalamic midline elicited labelling of striosomes and, invariably, ventral extrastriosomal matrix, the nucleus accumbens, and the amygdala. This projection was topographically organized: rostral thalamic deposits elicited labelling in the medial caudate nucleus and the medial nucleus accumbens. More caudal injections produced more lateral labelling. Lateral division: The lateral division is composed of at least three projection systems distinguished by their patterns of matrix innervation. Deposits involving the anterior intralaminar nuclei and the striatally projecting cells located lateral to the stria medullaris (anterior intralaminar complex) produced an even, diffuse labelling of the matrix tissue and weak labelling of the striosomes. Injections placed in the ventroanterior, ventrolateral, and ventromedial nuclei (rostral ventral complex) elicited fibrous labelling of matrix tissue that often showed nonstriosomal inhomogeneities. Deposits involving the centromedian and parafascicular nuclei (posterior intralaminar complex) produced a highly variable pattern of matrix labelling that included both homogeneous and decidedly patchy innervations of the extrastriosomal matrix. Each of these lateral thalamostriatal systems showed a similar spatial organization, whereby dorsoventral and mediolateral thalamic axes were roughly preserved in the projection to striatum.

Animals↗
PubMed1993

Evidence for a multi-compartmental histochemical organization of the nucleus accumbens in the rat.

In the present study, the compartmental organization of the nucleus accumbens was investigated by comparing the pattern of leu-enkephalin immunoreactivity with that of the opioid receptor ligand, naloxone, an established marker for the compartmental organization of the neostriatum. Both patterns have a nonhomogeneous, patch-like appearance throughout the rostrocaudal extent of the nucleus and show a good, mutual correspondence. In the core of the nucleus accumbens as well as in the border region between the nucleus accumbens and the caudate-putamen, leu-enkephalin-rich areas are in register with opioid receptor-dense areas. In the shell region the precise relationship between the enkephalin and the naloxone patterns could not be established. A comparison of the connectivity patterns and neurochemical characteristics of the opioid receptor-dense compartments in the nucleus accumbens with those in the caudate-putamen reveals major discrepancies between these two striatal subdivisions. We therefore conclude that, rather than a bicompartmental patch/striosome-matrix organization, the nucleus accumbens has a multicompartmental organization.

Animals↗
PubMed2004

The existence of biexponential signal decay in magnetic resonance diffusion-weighted imaging appears to be independent of compartmentalization.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10,000 mm(-2) s) under intact, global ischemic, and cold-injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron-microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples. The results suggest that compartmentalization is not an essential feature of biexponential decay in diffusion experiments.

Animals↗
PubMed1989

Nuclear magnetic relaxation studies of the compartmentalized water in crosslinked polymer gels.

Nuclear magnetic relaxation measurements of water in gels made of crosslinked dextran or polyacrylamide (water content, 30-60 wt%) were carried out using broad-line proton-pulsed NMR. Both T1 and T2 values showed inflection against pore size, i.e., the size of the compartment made by crosslinks of the polymer gels. T2 (or T1) values obtained for gels with compartments smaller than the critical size remained low within the range of the water content used in this experiment. Those values of gels with larger compartments, on the other hand, became higher with increasing size. When the size of the compartment was larger than the critical size, T1 and T2 values also became higher with increasing water content. The inflection point can be considered to correspond to the critical compartment size below which the motion of compartmentalized water in gels is more or less restricted. When the compartment is small, however, not only the effect of the molecular motion of water but also that of the proton exchange between compartmentalized water and gel matrix or hydration water should be taken into consideration for the interpretation of the short relaxation times observed, especially by T2. The results obtained in this investigation might provide useful information in the explanation and evaluation of the relaxation values in tissue.

Acrylic Resins↗
PubMed2001

The rise and fall of compartmental analysis.

The concept of compartment evolved in the contexts of radioactivity, physiology, pharmacology and tracer kinetics. Recently compartmental models have been compared with 'physiological models', even though in most cases the same, or stricter hypotheses, are necessary for the validity of these latter models. This paper shows that the methods of compartmental analysis are valid only if some specific hypotheses are valid.

Absorption↗
PubMed2002

Comparison of two compartmental models for describing ranitidine's plasmatic profiles.

The plasmatic profiles of 12 healthy volunteers after oral administration of ranitidine (150 mg) were studied considering two compartmental models. We observed the presence of two peaks. The proposed mechanism responsible for the existence of secondary peaks includes enterohepatic recirculation and the existence of multiple sites of absorption along the gastrointestinal tract. For characterizing the pharmacokinetic aspect of the drug, both phenomena were described using two compartmental models. We calculated the pharmacokinetic parameters and statistical tests after fitting the data of each volunteer under both models proposed. Statistically significant differences were not found in the statistical test values but existed in the area under the curve (AUC) comparing between models. To decide which of the two proposed models gave the best approximation of the physiological phenomenon undergone, we studied the pharmacokinetic of the drug in the rat, an animal without gallbladder. After oral administration of ranitidine, the plasmatic profile of the animals showed at least two peaks. Less than 0.2% of an oral dose was recovered in bile as ranitidine. Therefore, and considering the rat has no post-absorptive depot from where the drug can be released discontinuously, enterohepatic recycling does not seem to contribute significantly to the occurrence of secondary peaks in the concentration-time profiles of rats. Considering the results, we proposed that the best model able to explain the plasmatic profiles found in man and rats after oral administration of ranitidine is the one that presents multiple sites of absorption along the gastrointestinal tract. It is important to define the correct model in the calculation of the AUC and so in the value of the absolute bioavailability.

Adult↗