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PubMed1999

Vascular surgical society of great britain and ireland: transcranial doppler-directed dextran therapy in the prevention of postoperative carotid thrombosis

BACKGROUND: Evidence suggests that embolization precedes carotid thrombosis, a previously unpredictable event complicating 2-3 per cent of all carotid endarterectomies. It was hypothesized that dextran 40 therapy might prevent progression to complete thrombosis in high-risk patients. METHODS: Between October 1995 and July 1998, 400 consecutive patients were monitored following carotid endarterectomy using transcranial Doppler ultrasonography. Those with sustained embolization (more than 25 in 10 min) or those with emboli that distorted the middle cerebral artery waveform were commenced on an incremental dextran 40 infusion. RESULTS: Two hundred and sixteen patients (54 per cent) had one or more emboli detected (96 per cent within 2 h of flow restoration) but only 15 (4 per cent) required dextran therapy. Embolization ceased in each case although the dextran dose had to be adjusted in four. In one of the latter patients, embolization recurred on day 5 but was again controlled with high-dose dextran. Overall, the death and any stroke rate was 2 per cent and no patient suffered a stroke due to carotid thrombosis. CONCLUSION: A few patients develop sustained embolization following carotid endarterectomy which, in previous studies, has been shown to be highly predictive of carotid thrombosis. The authors' experience to date suggests that dextran can stop this phase of embolization and prevent progression to complete carotid thrombosis. However, the dose of dextran has to be adjusted in 25 per cent of patients (i.e. blind administration of dextran may not be effective) and, very rarely, embolization may recur later.

Journal Article↗

PubMed1999

Vascular surgical society of great britain and ireland: platelet function during carotid endarterectomy and the antiplatelet effect of dextran 40

BACKGROUND: Dextran 40 has been shown to reduce cerebral embolization following carotid endarterectomy (CEA). This study aimed to determine changes in platelet function during CEA and the antiplatelet effect of dextran 40. METHODS: Platelet function was measured by whole-blood flow cytometry in the peripheral arterial blood of patients during CEA and 24 h later. The binding index of P-selectin and PAC-1 expression were measured as markers of activation and aggregation. Patients were kept on aspirin 75-150 mg until the day of surgery and received an intravenous bolus of 5000 units unfractionated heparin before carotid artery clamping. High-intensity transient signals (HITS) in the ipsilateral middle cerebral artery were measured with transcranial Doppler (TCD) ultrasonography before, during and after operation. Results are presented as median (interquartile range) and statistical significance was determined using the Mann-Whitney U test. RESULTS: Thirty-eight patients undergoing CEA were studied. The P-selectin binding index rose significantly from incision (0.9 (0.2-2.7)) after carotid clamping (1.5 (0.6-3.6); P < 0.01), clamp release (1.7 (0. 3-3.0); P < 0.01), 1 h after operation (1.5 (0.3-2.6); P < 0.05) and 24 h after operation (1.3 (0.6-2.5); P < 0.05). PAC-1 binding index increased from incision (0.4 (0.1-0.8)) after carotid clamping (2.0 (0.4-4.2); P < 0.01) and clamp release (1.8 (0.3-2.9); P < 0.05). TCD monitoring showed an increase in preoperative HITS per 30 min (2 (0-3)) during dissection (8 (1-15); P < 0.05), after clamp release (16 (2-27); P < 0.01) and during recovery (10 (2-29); P < 0.01). After operation, patients with more than 50 HITS per 30 min were started on an infusion of dextran 40. Six patients had a dextran 40 infusion. The P-selectin binding index decreased from 1.6 (0.7-1.9) to 0.6 (0.3-1.5) 1 h after dextran (P < 0.05) and 0.1 (0.1-0.2) 24 h after dextran (P < 0.05). PAC-1 expression decreased from 0.4 (0.3-0. 5) to 0.1 (0.1-0.1) 24 h after dextran (P < 0.05). CONCLUSION: Significant platelet activation and aggregation occurs during CEA despite the use of antiplatelet treatment. A simultaneous increase in HITS was demonstrated with TCD. Dextran 40 was shown to have an antiplatelet effect after CEA; this is further evidence that it may have a role in reducing thromboembolic complications.

Journal Article↗

PubMed1997

Effect of dextran 70 blood substitute on diazepam binding by human serum albumin.

Diazepam binding studies with dextran 70 and human serum albumin (HSA) were carried out using centrifugation and a membrane ultrafiltration technique to separate the drug protein complex and the free microsolute. The molecular filtration method was found to be precise and reproducible with very little variations. The binding of diazepam to dextran was significant but considerably smaller when compared with the extensive binding of diazepam to HSA. The results of these studies demonstrate that diazepam binding of HSA is altered in the presence of dextran. Diazepam binds to dextran resulting in displacement of diazepam from albumin binding sites. The contributing effect of dextran to overall diazepam binding increased as the dextran concentration increased and the HSA concentration decreased. However, the net result of HSA dilution with dextran 70 was still an increase in the percent free diazepam. Various concentrations of dextran 70 significantly displaced HSA bound diazepam in all the mixtures studied.

Journal Article↗

PubMed1984

Effects of DEAE-dextran on infection and hemolysis by VSV. Evidence that nonspecific electrostatic interactions mediate effective binding of VSV to cells.

The polycation DEAE-dextran increased the binding of VSV to BHK cells about fourfold over a wide range of VSV concentrations. The same proportion of bound virions was internalized by the cell in the presence or absence of DEAE-dextran. Viral primary RNA production was increased to the equivalent of a 4- to 4.5-fold increase in multiplicity of infection in the presence of DEAE-dextran, closely paralleling the increase in total VSV binding to the cell. Viral secondary RNA production was increased only to the equivalent of about twofold increase in multiplicity. The kinetics of both primary and secondary RNA production were indistinguishable in the presence or absence of DEAE-dextran. DEAE-dextran had to be present simultaneously with the input virions in order to enhance RNA production; addition even 30 min after infection was ineffective. Addition of the polycation DEAE-dextran was also required for appreciable VSV-induced hemolysis of human erythrocytes; erythrocytes of several other species were hemolyzed in the absence of DEAE-dextran, but hemolysis was enhanced by its presence. Maximal binding and hemolysis occurred at pH 5.0 and 37 degrees. Vesicles containing only G protein and viral lipid were 40% as hemolytic as intact virions at pH 5.0, but were inactive at pH 6.0; "spikeless" virions lacking G, or protein-free viral lipid vesicles were not hemolytic, showing that G protein is necessary for hemolysis. These results, together with other recent observations, suggest that multiple electrostatic interactions between VSV and the cell surface, rather than an affinity for specific surface molecules, mediated the productive (infection producing) binding of VSV to the cell surface.

Animals↗

PubMed1983

Carcinogenicity of dextran sulfate sodium in relation to its molecular weight.

The carcinogenicity of dextran and 3 kinds of dextran sulfate sodium with different molecular weights and almost the same sulfur content were compared in ACI rats. Dextran sulfate sodium of molecular weight 54,000 showed a strong carcinogenic activity when it was given orally as 2.5% diet, whereas dextran sulfate sodium of molecular weight 520,000 and 9500 and dextran showed no significant carcinogenicity, i.e. the peak of carcinogenic activity of dextran sulfate sodium appeared at molecular weight 54,000, and dextran sulfates with larger or smaller molecular weights had no carcinogenic activity.

Adenocarcinoma↗

PubMed1992

Molecular interaction between HIV-1 major envelope glycoprotein and dextran sulfate.

We investigated at the molecular level the interaction between, HIV-1 recombinant gp160 (rgp160) and low-molecular-weight dextran sulfate. We demonstrate the occurrence of a specific interaction between rgp160 and sulfated dextran beads, which is saturable, pH-dependent and inhibitable by soluble dextran sulfate but not by soluble dextran. This specific interaction has a low affinity, with an estimated Kd in the 10(-4) M range. In addition, the binding of rgp160 to soluble recombinant CD4 (sT4) can only be inhibited by the preincubation of rgp160, but not of sT4, with dextran sulfate. Taken together, these results demonstrate the occurrence of a low affinity, but specific interaction between dextran sulfate and rgp160. This may account, at least in part, for the anti-HIV-1 activity of dextran sulfate.

CD4 Antigens↗

PubMed1990

Effect of dextran sulfate on renal accumulation of gentamicin.

The effect of dextran sulfate of three molecular weights (1000, 5000, and 90,000) on the accumulation of gentamicin in rat kidney was investigated using a continuous infusion technique. During the infusions of both gentamicin and gentamicin-dextran sulfate mixtures, the gentamicin plasma concentration was maintained at 10 microgram/ml. The renal cortical accumulation of gentamicin was significantly lower when dextran sulfate (1000, 5000) was coadministered. The inhibition of cortical gentamicin accumulation increased with increasing dextran sulfate dose, and it was proportional to the amount of dextran sulfate excreted into the urine. Analysis by electrophoresis on cellulose acetate membrane indicated that gentamicin binds to dextran sulfate in rat urine. Therefore, gentamicin-dextran sulfate binding within the lumen of the proximal tubules may reduce the renal reabsorption and possibly the renal toxicity of gentamicin.

Animals↗

PubMed1990

[Effects of DEAE-dextran, centrifugation, cycloheximide and their combination on infection and growth of Chlamydia psittaci bird isolates].

In order to establish a stable and uniform cultural method in a cell line HaLa 229, we studied the effect of DEAE-dextran, centrifugation, cycloheximide and their combination on infectivity and progeny yields of Chlamydia psittaci isolated mainly from birds. Of 11 strains (10 avian and one human origin Ito strain), 9 showed maximal inclusion formation when host cells were treated with a combination of dextran and cycloheximide. Of the other two strains, one showed maximum inclusion formation with dextran alone and any treatments did not enhance the inclusion formation in another strain. Maximal yields of progeny at 48 hours after infection was observed in 5 (4 avian and Ito) strains when host cells were treated with a combination of dextran and cycloheximide. One avian strain showed maximal yields with a triple treatment; dextran and cycloheximide combined with centrifugation. At 72 hours after infection, three avian and Ito strains showed maximal yields with a double treatment (dextran and cycloheximide) and other two avian strains showed that with a triple treatment (double treatment added with centrifugation). The results suggest that in a cell culture HeLa 229, the treatment with dextran and cycloheximide may provide an efficient isolation and growth pattern for most strains originated from birds.

Animals↗

PubMed1997

Binding, internalization and degradation of EGF-dextran conjugates in two human bladder-cancer cell lines.

Bladder carcinomas often have an increased number of epidermal growth factor (EGF) receptors. The EGF receptors can, in these cases, be targets for toxic conjugates. In this study, EGF-dextran conjugates were used as targeting agents with therapeutic potential. The binding, internalization and degradation of 125I-EGF-dextran conjugates in J82 and RT4, 2 different bladder cancer cell lines, were investigated. The behaviour of 125I-EGF was studied as a comparison. The 125I-EGF-dextran showed a continuous increase in binding up to 24 hr, while 125I-EGF exhibited maximum binding after about 90 min. Both cell lines showed similar binding patterns. The binding of 125I-EGF-dextran and 125I-EGF was, on both cell lines, receptor-specific since the binding could be displaced with non-radioactive EGF. Analysis of internalized and membrane-bound 125I activity after administration of 125I-EGF-dextran showed that most of the activity was membrane-bound. A large part of both the internalized and the membrane-bound activity remained cell-associated up to 24 hr. The internalized and membrane-bound activity after administration of 125I-EGF decreased rapidly and only a small fraction remained cell-associated after 24 hr. 125I-EGF-dextran remained cell-associated, with only a limited release of low- and high-molecular-weight radioactivity throughout the 24-hr period, while 125I-EGF was extensively degraded and released into the incubation medium as low-molecular-weight radioactivity during this time. Several qualities of the 125I-EGF-dextran conjugates might be favourable for targeted radiotherapy.

Cell Membrane↗

PubMed2000

Vitreal elimination kinetics of large molecular weight FITC-labeled dextrans in albino rabbits using a novel microsampling technique.

A novel sampling technique that allowed for continuous vitreal sampling of high molecular weight compounds was developed. This technique generated consistent and reproducible results. Fluorescein isothiocyanate-linked dextrans (FITC-dextrans) with average molecular weights of 4.4, 9.3, and 38.9 kD were selected for the study. A 100 microgram dose was administered into the vitreous by a short-term infusion (100 microL) over a period of 45 s, and sampling was carried out for 10 h. The vitreal elimination of these dextrans was found to follow apparent first-order elimination kinetics, having half-lives of 246 min, 275 min, and 484 min, respectively. Aqueous levels were also determined at the end of 10 h and were correlated with vitreal dextran concentrations. The FITC-dextrans displayed an initial equilibration phase of about 200 min followed by linear first-order elimination. Apparent diffusion coefficients in the vitreous have been calculated to be 7.56 x 10(-6) and 6.18 x 10(-6) cm(2)/s for 4.4 and 9.3 kD dextrans, respectively. Furthermore, it became evident that with progressively higher molecular weight FITC-dextrans the vitreal elimination rate constant gradually decreased. The elimination rate constant was found to be inversely related to the logarithm of molecular weight with a correlation coefficient of 0.983. Results obtained suggest an elimination mechanism primarily involving the transretinal route possibly with some involvement of the aqueous pathway.

Animals↗

PubMed2001

Immobilized RGD peptides on surface-grafted dextran promote biospecific cell attachment.

Dextran has recently been investigated as an alternative to poly(ethylene glycol) (PEG) for low protein-binding, cell-resistant coatings on biomaterial surfaces. Although antifouling properties of surface-grafted dextran and PEG are quite similar, surface-bound dextran has multiple reactive sites for high-density surface immobilization of biologically active molecules. We recently reported nontoxic aqueous methods to covalently immobilize dextran on material surfaces. These dextran coatings effectively limited cell adhesion and spreading in the presence of serum-borne cell adhesion proteins. In this study we utilized the same nontoxic aqueous methods to graft cell adhesion peptides on low protein-binding dextran monolayer surfaces. Chemical composition of all modified surfaces was verified by X-ray photoelectron spectroscopy (XPS). Surface-grafted cell adhesion peptides stimulated endothelial cell, fibroblast, and smooth muscle cell attachment and spreading in vitro. In contrast, surface-grafted inactive peptide sequences did not promote high levels of cell interaction. Surface-grafted high affinity cyclic RGD peptides promoted cell type-dependent interactions. With dextran-based surface coatings, it will be possible to develop well-defined surface modifications that promote specific cell interactions and perhaps better performance in long-term biomaterial implants.

3T3 Cells↗

PubMed1994

Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific delivery: steady-state pharmacokinetics in the rat.

Chronic colitis, e.g., ulcerative colitis and Crohn's disease, is presently treated with glucocorticoids and other antiinflammatory agents. Side-effects limit chronic glucocorticoid therapy. The dose, and consequently the side-effects, may be reduced by using prodrugs that selectively deliver drug to the colon. We previously synthesized glucocorticoid-dextran conjugates in which dexamethasone was attached to dextran (weight-average molecular weight = 72,600) using dicarboxylic acid linkers (succinate and glutarate). In the present study, dexamethasone-succinate-dextran and dexamethasone-glutarate-dextran were administered to two groups of male Sprague-Dawley rats by intragastric infusion. In two additional groups, disodium dexamethasone phosphate and dexamethasone hemisuccinate were each administered by subcutaneous infusion. In a fifth group, dexamethasone was administered by intragastric infusion. All groups were infused for sufficient time for steady state to be achieved. Colon-specific delivery was quantified using a drug-delivery index (DDI) in which steady-state dexamethasone concentrations in the cecum and colon were compared with those measured in blood after separate administrations of dexamethasone and dexamethasone-dextran conjugate. The colonic DDI values for dexamethasone-succinate-dextran and dexamethasone-glutarate-dextran were approximately seven and four, respectively. These values were a result of higher tissue concentrations and lower blood concentrations of dexamethasone after intragastric administration of the conjugates compared to subcutaneous and intragastric administration of dexamethasone. The pharmacokinetics of methyl-prednisolone was also investigated after subcutaneous infusion. Observed cecal and colonic tissue-to-blood ratios of 19:1 and 12:1, respectively, showed that this drug is extensively delivered to the large intestine even after subcutaneous administration.

Animals↗

PubMed1992

Derivatized dextrans mimic heparin as stabilizers, potentiators, and protectors of acidic or basic FGF.

Acidic and basic fibroblast growth factors (aFGF and bFGF) belong to a family of structurally related polypeptides characterized by a high affinity for heparin. a and bFGF display mitogenic activity for many cell types. Biological activity is strongly potentiated by heparin which stabilizes their molecular conformation by preventing physicochemical or enzymatic degradation. In our previous study we have shown that a water-soluble derivatized dextran named DDE, containing 82.2% methyl carboxylic acid groups, 6.1% benzylamide, and 5.6% sulfonate with a specific anticoagulant activity equivalent to heparin of 0.5 IU/mg could potentiate the mitogenic activity of aFGF on CCL39 cells. Optimal concentrations for maximal potentiation of 400 micrograms/ml and 20 micrograms/ml were obtained respectively for DDE and heparin. In the present report, we have uncovered the fact that several carboxymethyl benzylamide sulfonate dextrans differing in degree and positioning of the substituent groups can mimic heparin in regard to the protection, stabilization, and potentiating effects with aFGF or bFGF. Our data establishes that the dextran derivatives studied can act as potentiating agents for FGFs. Native dextran (DDA) had no effect. Dextran derivatives can also protect aFGF and bFGF from heat as well as from pH denaturation, and against trypsic and chymotrypsic degradation. The dextran derivative DDI (82% methylcarboxylic acid, 23% benzylamide, 13% sulfonate) was studied in greater detail and exhibited a greater protection for bFGF and a lesser protecting effect for aFGF than heparin. Derivatized dextrans which have very weak anticoagulant activity are of great interest as alternatives to heparin for use as stabilizers, potentiators, protectants, and slow-release matrices for FGFs in pharmaceutical formulations.

Animals↗

PubMed1991

Characterization and differentiation of some complex dextran sulfate preparations of medicinal interest.

Dextran sulfate samples from different sources were examined by 1H and 13C NMR spectroscopy to differentiate the samples on the basis of extent and sites of sulfation. The anomeric (H-1) signal proved to be a good indicator ranging from no sulfation (as in dextran) to virtually complete sulfation at positions 2 and 3, whereas the relative intensity of the H-4 signal afforded a measure, conversely, of the degree of sulfation at position 4. Three different dextran sulfate tablet formulations were found by NMR to contain similar dextran sulfate material that was characterized by a high degree of sulfation at positions 2 and 3. Position 4 of dextran appears to be less readily amenable to substitution. Quasi-elastic light scattering (QELS) analysis of aqueous dispersions of the bulk dextran sulfate samples and formulated tablets permitted additional particle size and homogeneity differentiation. None of the dextran sulfate materials showed either anti-factor Xa activity or marked anticoagulant activity.

Anticoagulants↗

PubMed1994

Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific delivery: hydrolysis in rat gastrointestinal tract contents.

Chronic colitis, e.g., ulcerative colitis and Crohn's disease, is presently treated with glucocorticoids and other antiinflammatory agents. Side effects limit chronic glucocorticoid therapy. The dose, and consequently the side effects, may be reduced by using prodrugs that selectively deliver drug to the colon. We previously synthesized glucocorticoid-dextran conjugates in which dexamethasone and methylprednisolone were attached to dextran (weight-average molecular weight = 72,600) using dicarboxylic acid linkers (succinate and glutarate). In the present study, the hydrolysis kinetics of the hemiesters (hemiester = glucocorticoid+linker) and dextran conjugates were determined after incubation at 37 degrees C in diluted luminal contents of the gastrointestinal (GI) trace of male Sprague-Dawley rats. The hemiesters were rapidly hydrolyzed in the proximal small intestine (e.g., dexamethasone-hemiglutarate t1/2 = 0.5 h). This rate decreased progressively down the GI tract (t1/2 = 4.8, 54, and 68 h in distal small intestine, cecum, and colon, respectively). The enzyme responsible for hemiester hydrolysis, apparently a type-A alkaline carboxylesterase, is probably of host origin because its activity is highest in the small intestine where bacterial count is low. The dextran conjugates resisted hydrolysis in upper GI tract contents but were rapidly degraded in cecal and colonic contents where the bacterial count is high. The dextran conjugate tested, methylprednisolone-succinate-dextran, was easily hydrolyzed by an endodextranase, indicating that substrate specificity is not lost upon the attachment of glucocorticoid. The results of this study indicate that dextran conjugates may be useful in selectively delivering glucocorticoids to the large intestine for the treatment of colitis.

Anaerobiosis↗

PubMed2006

Comparative study of isovolemic hemodilution with 3% albumin, dextran-40, and prophylactic enoxaparin (LMWH) on thrombus formation at venous microanastomosis in rats.

The objective of the present investigation was to compare the effect of isovolemic hemodilution with 3% albumin, dextran-40, and enoxaparin on the prevention of thrombosis in femoral vein microanastomosis using an experimental model in rats. Forty male Wistar rats were allocated into four groups: group 1, control, thrombogenic model without previous treatment; group 2, hemodiluted, thrombogenic model with previous hemodilution; group 3, dextran-40, thrombogenic model with dextran infusion (10 ml/kg), and group 4, enoxaparin, thrombogenic model with administration of enoxaparin (0.5 mg/kg/day). Hemostatic parameters, hematologic examinations, patency of anastomosis, and histopathological examination were evaluated. The hemostatic parameters were similar in the four groups studied. Group hemodiluted, dextran-40, and enoxaparin showed significantly reduced number of red blood cells and platelets as compared with the control group. The hemodilution significantly increased the patency rates of the vein at 20 min and 48 h. Dextran-40 and enoxaparin improved the patency of the vein only at 20 min, but failed to show a significant increase in the final patency at 48 h. After 48 h, the rate of venous thrombosis, as evaluated microscopically, was significantly decreased in hemodiluted animals (1/8) as compared with controls (10/10); in rats treated with dextran-40 (7/10) and enoxaparin (5/10) the rate of venous thrombosis was significantly higher as compared with rats of the group hemodiluted. Based on these observations, it can be concluded that hemodilution with albumin 3% was a safe and more adequate procedure than the use of the schemes of administration of dextran-40 and enoxaparin used in this study to prevent thrombus formation at femoral vein microanastomosis in rats. Since hemodilution promotes reduction in blood viscosity and in erythrocyte and platelet aggregation as well as dilution of the coagulation factors themselves, its use could provide better microcirculatory blood perfusion, decreasing the risk of thrombosis, and making possible safer microsurgical procedures.

Anastomosis, Surgical↗

PubMed1992

Dextrans as markers for endocytosis in innervated and denervated skeletal muscle.

Fluorescence-labeled dextrans were evaluated as markers for endocytosis in skeletal muscle. Fluorescein isothiocyanate (FITC)-labeled dextrans (average molecular weight 3900 to 71200) showed a higher uptake in denervated than in innervated muscle both in vitro and in vivo. The in vitro uptake of FITC-dextran (35.600) increased linearly with time at 37 degrees C, and was almost completely inhibited by low temperature (4 degrees C). The uptake was not a pure bulk uptake, because a saturable component was evident from the concentration dependence and from competition experiments with unlabeled dextran. The uptake of FITC-labeled or rhodamine B isothiocyanate (RITC)-labeled dextrans in denervated muscle occurred mainly in small segments of the fibers centered around the denervated endplate region. However, not all denervated fibers showed such segments. Periodic acid Schiff's base staining for carbohydrates stained dextrans in denervated muscle fibers. Some staining, probably of lysosomes, was also observed in denervated muscle not exposed to dextran.

Animals↗

PubMed2006

Modulatory effects of dextran sulfate and fucoidan on binding and channel properties of AMPA receptors isolated from rat brain.

Previous work showed that the glycosaminoglycan (GAG) dextran sulfate (500 kDa) altered the binding and channel properties of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. The current study compared the effects of dextran sulfate with another GAG, fucoidan (100-180 kDa), to determine whether GAG-mediated changes in high-affinity binding of AMPA receptors have a concomitant influence on specific channel properties. Dextran sulfate was more potent in inhibiting high-affinity AMPA binding to solubilized receptors (EC(50) of 7 nM) compared to fucoidan (EC(50) of 124 nM). Similarly, dextran sulfate was more potent in modulating the channel properties of purified and reconstituted AMPA receptors. Dextran sulfate, at 1 mug/ml (2 nM), produced a three to fourfold increase in open channel probability and a threefold increase in mean burst duration of channel activity elicited by 283 nM AMPA. The mean open time was increased by two to threefold and closed times were decreased by two to eightfold. Fucoidan produced similar effects at a concentration many times higher than that of dextran sulfate. Dextran sulfate and fucoidan had no effect on the single channel conductance or the ability of a specific antagonist to block AMPA channels. The effects of GAGs on multichannel patches showed an interactive channel gating behavior resulting in macroscopic currents with long lived open channel life times. These findings suggest that GAG components of proteoglycans can interact with and alter the binding affinity of AMPA receptors and modulate their functional properties.

Animals↗