Biomedical subjects

C M Carvalho

Publications and source records attributed to C M Carvalho.

At least 19 recordsLinked to original sources

PubMed2004

The movement protein of cowpea mosaic virus binds GTP and single-stranded nucleic acid in vitro.

The movement protein (MP) of Cowpea mosaic virus forms tubules in plasmodesmata to enable the transport of mature virions. Here it is shown that the MP is capable of specifically binding riboguanosine triphosphate and that mutational analysis suggests that GTP binding plays a role in the targeted transport of the MP. Furthermore, the MP is capable of binding both single-stranded RNA and single-stranded DNA in a non-sequence-specific manner, and the GTP- and RNA-binding sites do not overlap.

Animals↗

PubMed2003

The C-terminal region of the movement protein of Cowpea mosaic virus is involved in binding to the large but not to the small coat protein.

Cowpea mosaic virus (CPMV) moves from cell to cell as virus particles which are translocated through a plasmodesmata-penetrating transport tubule made up of viral movement protein (MP) copies. To gain further insight into the roles of the viral MP and capsid proteins (CP) in virus movement, full-length and truncated forms of the MP were expressed in insect cells using the baculovirus expression system. Using ELISA and blot overlay assays, affinity purified MP was shown to bind specifically to intact CPMV virions and to the large CP, but not to the small CP. This binding was not observed with a C-terminal deletion mutant of the MP, although this mutant retained the capacity to bind to other MP molecules and to form tubules. These results suggest that the C-terminal 48 amino acids constitute the virion-binding domain of the MP.

Animals↗

PubMed2001

Role of kainate receptor activation and desensitization on the [Ca(2+)](i) changes in cultured rat hippocampal neurons.

We investigated the role of kainate (KA) receptor activation and desensitization in inducing the increase in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) in individual cultured rat hippocampal neurons. The rat hippocampal neurons in the cultures were shown to express kainate receptor subunits, KA2 and GluR6/7, either by immunocytochemistry or by immunoblot analysis. The effect of LY303070, an alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, on the alterations in the [Ca(2+)](i) caused by kainate showed cell-to-cell variability. The [Ca(2+)](i) increase caused by kainate was mostly mediated by the activation of AMPA receptors because LY303070 inhibited the response to kainate in a high percentage of neurons. The response to kainate was potentiated by concanavalin A (Con A), which inhibits kainate receptor desensitization, in 82.1% of the neurons, and this potentiation was not reversed by LY303070 in about 38% of the neurons. Also, upon stimulation of the cells with 4-methylglutamate (MGA), a selective kainate receptor agonist, in the presence of Con A, it was possible to observe [Ca(2+)](i) changes induced by kainate receptor activation, because LY303070 did not inhibit the response in all neurons analyzed. In toxicity studies, cultured rat hippocampal neurons were exposed to the drugs for 30 min, and the cell viability was evaluated at 24 hr using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The selective activation of kainate receptors with MGA, in the presence of Con A, induced a toxic effect, which was not prevented by LY303070, revealing a contribution of a small subpopulation of neurons expressing kainate receptors that independently mediate cytotoxicity. Taken together, these results indicate that cultured hippocampal neurons express not only AMPA receptors, but also kainate receptors, which can modulate the [Ca(2+)](i) and toxicity.

Animals↗

PubMed2001

Inhibition of glutamate release by BIA 2-093 and BIA 2-024, two novel derivatives of carbamazepine, due to blockade of sodium but not calcium channels.

We investigated the mechanism(s) of action of two new putative antiepileptic drugs (AEDs), (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-024), by comparing their effects on the release of endogenous glutamate in hippocampal synaptosomes, with those of carbamazepine (CBZ) and oxcarbazepine (OXC). The AEDs inhibited the release of glutamate evoked by 4-aminopyridine (4-AP) or veratridine in a concentration-dependent manner, being CBZ more potent than the other AEDs. Using conditions of stimulation (30 mM KCl), where Na(+) channels are inactivated, the AEDs did not inhibit either the Ca(2+)-dependent or -independent release of glutamate. The results indicate that BIA 2-093 and BIA 2-024 have sodium channel-blocking properties, but CBZ and OXC are more potent than the new AEDs. Moreover, the present data also indicate that Ca(2+) channels coupled to the exocytotic release of glutamate and the activity of the glutamate transporter were not affected by the AEDs.

Analysis of Variance↗

PubMed2001

Presynaptic N-methyl-D-aspartate receptor activation inhibits neurotransmitter release through nitric oxide formation in rat hippocampal nerve terminals.

In brain synapses, nitric oxide synthase activation is coupled to N-methyl-D-aspartate-mediated calcium entry at postsynaptic densities through regulatory protein complexes, however a presynaptic equivalent to this signaling mechanism has not yet been identified. Novel evidence indicates that N-methyl-D-aspartate glutamate receptors may play a presynaptic role in synaptic plasticity. Thus, we investigated whether ionotropic glutamate receptor activation in isolated nerve terminals regulates neurotransmitter release, through nitric oxide formation. N-Methyl-D-aspartate dose-dependently inhibited the release of glutamate evoked by 4-aminopyridine (IC(50)=155 microM), and this effect was reversed by the N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphopentanoic acid and by the nitric oxide synthase inhibitor, L-nitroarginine, in synaptosomes isolated from whole hippocampus, CA3 and CA1 areas, but not from the dentate gyrus. In contrast, the 4-aminopyridine-evoked release of glutamate was reduced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate by a nitric oxide-independent mechanism, since it was not blocked by L-nitroarginine, and N-methyl-D-aspartate, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate, significantly increased cGMP formation. Presynaptic N-methyl-D-aspartate receptors are probably involved since removing extracellular nitric oxide with the scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide did not block the depression of glutamate release by N-methyl-D-aspartate. The mechanism underlying this depression involves the inhibition of synaptic vesicle exocytosis since N-methyl-D-aspartate/nitric oxide inhibited the release of [3H]glutamate and [14C]GABA evoked by hypertonic sucrose. The results also suggest that presynaptic N-methyl-D-aspartate receptors may function as auto- and heteroreceptors.

4-Aminopyridine↗

PubMed2001

A continuous membrane bioreactor for ester synthesis in organic media: II. Modeling Of MBR continuous operation.

A model was developed to describe the conversion degree in a membrane bioreactor (MBR) for the synthesis of short-chain esters as a function of the flow rate. The transesterification reaction was catalyzed by a recombinant cutinase of Fusarium solani pisi microencapsulated in reversed micelles of AOT/isooctane. The differences of product concentration in permeate and retentate together with the deactivation profiles led to an enzyme distribution evaluation that describes the experimental values attained. The model considers the bioreactor design as well as its hydrodynamics and the enzyme kinetics. The approach included the analysis of the MBR operation as a CSTR, a PFR, and a series of continuous reactors. The comparative efficiency of these reactor types is discussed. The enzyme distribution was estimated for all the cases. The best description was obtained considering a series of two CSTRs. The modeling results led to a re-evaluation of cutinase operational stability. Deactivation rates correlated very well with the hydrodynamic aspects of biocatalyst location.

Bioreactors↗

PubMed2001

A continuous membrane bioreactor for ester synthesis in organic media: I. Operational characterization and stability.

The feasibility of continuous ester synthesis in a membrane bioreactor (MBR) by a recombinant cutinase from Fusarium solani pisi was investigated, using the optimal conditions previously attained by medium engineering. The objective was to analyze the MBR behavior as a differential or an integral reactor. The main component of the reactor was an anisotropic ceramic membrane with 15,000 NMWCO. The operating variables included the influence of substrates ratio and flow rate on the conversion degree and on the productivity. The highest conversion degree was obtained using 1M of hexanol and 0.1M of butyl acetate as acyl donor. The use of these substrate concentrations led to a conversion degree of 79.3% and a specific productivity of 41 g hexyl acetate/(d x g cutinase), when the permeate flow rate was 0.025 mL/min. The increase of flow rate to 0.4 mL/min decreased the conversion to 35.6%, although the productivity was enhanced to 294 g product/day x g enzyme. The MBR characterization involved the calculations of mass balance, recirculation rate, conversion per pass, number of cycles, and hydraulic residence time. The operational stability was also evaluated in a longterm experiment over 900 hours and the enzyme half-life was estimated to be approximately 2 years.

Acetates↗

PubMed2001

Abnormal expression of MDM2 in prostate carcinoma.

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.

Adenocarcinoma↗

PubMed2001

Modulation of intracellular calcium changes and glutamate release by neuropeptide Y1 and Y2 receptors in the rat hippocampus: differential effects in CA1, CA3 and dentate gyrus.

In the present work, we investigated the role of pre- and post-synaptic neuropeptide Y1 (NPY1) and Y2 receptors on the calcium responses and on glutamate release in the rat hippocampus. In cultured hippocampal neurones, we observed that only NPY1 receptors are involved in the modulation of intracellular free calcium concentration ([Ca(2+)](i)). In 88% of the neurones analysed, the increase in the [Ca(2+)](i), in response to depolarization with 50 mM KCl, was inhibited by 1 microM [Leu31,Pro34]NPY, whereas 300 nM NPY13-36 was without effect. However, studies with hippocampal synaptosomes showed that both NPY1 and Y2 receptors can modulate the [Ca(2+)](i) and glutamate release. The pharmacological characterization of the NPY-induced inhibition of glutamate release indicated that Y2 receptors play a predominant role, both in the modulation of Ca(2+)-dependent and -independent glutamate release. However, we could distinguish between Y1 and Y2 receptors by using [Leu31,Pro34]NPY and NPY13-36. Active pre-synaptic Y1 receptors are present in the dentate gyrus (DG) as well as in the CA3 subregion, but its activity was not revealed by using the endogenous agonist, NPY. Concerning the Y2 receptors, they are present in the three subregions (CA1, CA3 and DG) and were activated by either NPY13-36 or NPY. The present data support a predominant role for NPY2 receptors in mediating NPY-induced inhibition of glutamate release in the hippocampus, but the physiological relevance of the presently described DG and CA3 pre-synaptic NPY1 receptors remains to be clarified.

Animals↗

PubMed2000

Neurotoxic/neuroprotective profile of carbamazepine, oxcarbazepine and two new putative antiepileptic drugs, BIA 2-093 and BIA 2-024.

We investigated and compared the toxicity profile, as well as possible neuroprotective effects, of some antiepileptic drugs in cultured rat hippocampal neurons. We used two novel carbamazepine derivatives, (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b, f]azepine-5-carboxamide (BIA 2-093) and 10, 11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-024), and compared their effects with the established compounds carbamazepine and oxcarbazepine. The assessment of neuronal injury was made by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay, as well as by analysing morphology and nuclear chromatin condensation (propidium iodide staining), after hippocampal neurons were exposed to the drugs for 24 h. The putative antiepileptic drugs, BIA 2-093 or BIA 2-024 (at 300 microM), only slightly decreased MTT reduction, whereas carbamazepine or oxcarbazepine were much more toxic at lower concentrations. Treatment with the antiepileptic drugs caused nuclear chromatin condensation in some neurons, which is characteristic of apoptosis, and increased the activity of caspase-3-like enzymes, mainly in neurons treated with carbamazepine and oxcarbazepine. The toxic effect caused by carbamazepine was not mediated by N-methyl-D-aspartate (NMDA) or by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptors. Moreover, the antiepileptic drugs failed to protect hippocampal neurons from the toxicity caused by kainate, veratridine, or ischaemia-like conditions.

Animals↗

PubMed2000

Kinetics of cutinase catalyzed transesterification in AOT reversed micelles: modeling of a batch stirred tank reactor.

A transesterification process is analyzed in its multiple kinetic components that include the determination of the kinetic constants for both substrates, butyl acetate (BAc) and hexanol (H), involved in the alcoholysis reaction and for the products formed (hexyl acetate (HAc) and butanol (B)), participating into the reverse reaction. The order of magnitude of these constants is discussed in relation with the AOT/isooctane reverse micellar system under study. The values of the equilibrium conversion (X(e)) and constant (K(eq)) were also determined. Diffusional limitations were detected for H concentrations lower than 450 mM and the correspondent effectiveness factors were calculated. Above 450 mM H the reaction is kinetically controlled. The operation of a batch stirred tank reactor (BSTR) was modeled considering the integrated rate equation for reversible kinetics.

Acetates↗

PubMed2000

Reverse micelles as reaction media for lipases.

Reversed micelles are at the present time faced as common organic media to perform biocatalysis. They have been associated to the idea of a microreactor where the enzyme can be sheltered and protected from solvent detrimental effects. This simplistic idea led some investigators to ignore some basic understanding, such as the recognition of the enzyme-specific microenvironment and what the enzyme experiences inside the reversed micelle. To date the number of reactions catalyzed by lipases in reversed micelles is large. This review aims to highlight some of the fundamental aspects of the lipase microencapsulation as well as to resume the outstanding progress of the reversed micellar systems. The properties of the micellar microenvironment are reviewed and related to the lipases' performance both in terms of activity and stability. The heterogeneity of reversed micellar systems is discussed in relation to component distribution models and also to enzymatic kinetics. The new trends and the practical aspects where efforts should be centralized in order to spread out the micellar bioreactor technology over industrial processes are also discussed.

Catalysis↗

PubMed2000

Role of desensitization of AMPA receptors on the neuronal viability and on the [Ca2+]i changes in cultured rat hippocampal neurons.

We investigated the role of desensitization of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptors on the neurotoxicity and on the [Ca2+]i changes induced by kainate or by AMPA in cultured rat hippocampal neurons. The neuronal viability was evaluated either by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, or by analysis of cell morphology. Short-term exposure of the neurons to kainate or AMPA (30 min) was not toxic, but the exposure for 24 h to the excitotoxic drugs caused a concentration-dependent neurotoxic effect which was prevented by LY 303070, a noncompetitive AMPA receptor antagonist. In the presence of cyclothiazide (CTZ), kainate or AMPA was toxic (30 min exposure), or the toxic effect was significantly enhanced (24 h exposure), but in this case LY 303070 did not completely protect the cells against kainate-induced toxicity. The alterations in the [Ca2+]i caused by kainate or AMPA showed a great cell-to-cell variability. LY 303070 completely or partially inhibited the responses stimulated by kainate. CTZ differentially affected the responses evoked by kainate or AMPA. In the majority of hippocampal neurons, CTZ did not potentiate, or only slightly potentiated, the kainate-stimulated responses but in 11% of neurons there was a great potentiation. In AMPA-stimulated neurons, the responses were slightly or greatly potentiated in the majority of neurons, but not in all of them. The results show that AMPA and kainate may be toxic, depending on the time of exposure and on the blockade of the desensitization of the AMPA receptors. Overall, our results clearly show that there exist different populations of hippocampal neurons with different sensitivities to kainate, AMPA, CTZ and LY 303070. Moreover, the effects of CTZ on both [Ca2+]i alterations and neurotoxicity are not fully correlated.

Animals↗

PubMed2000

Monoclonality of asynchronous bilateral lymphoma of the testis.

OBJECTIVES: Lymphoma is the most frequent testicular malignancy in men over 60 years of age. Even though patients present initially with localized disease, the high incidence of bilateral involvement, synchronous or not, and early systemic dissemination are characteristic of these neoplasms. Sometimes the interval between tumor involvement of both testes is long. The question is raised whether either the patient has a predisposition to present new clones of transformed lymphocytes, or the same disease using the same pathway from a systemic reservoir infiltrates the contralateral testis. METHOD: Polymerase chain reaction and DNA sequencing were used to detect immunoglobulin heavy chain (IgH) rearrangement in paraffin-embedded specimens from asynchronous tumors affecting the right and left testis of a 85-year-old man with an interval period of 13 months. RESULTS: Both tumors showed the same IgH rearrangement. CONCLUSIONS: The lymphoma affecting the left and right testis derived from the same clone. It makes a strong case that lymphoma of the testis is the first manifestation of a systemic disease and should be treated aggressively early at the beginning of the disease.

Aged↗

PubMed1999

Detection of fetal fibronectin in twin pregnancies in relation to gestational age.

CONTEXT: The presence of fetal fibronectin in the cervix or vagina has been investigated as a possible marker for the risk of preterm birth. Fetal fibronectin in cervical fluid can provide direct evidence of pathologic changes at the interface of fetal and maternal tissues. OBJECTIVE: To evaluate the presence of fetal fibronectin as a predictor of premature delivery in twin pregnancies in relation to gestational age. DESIGN: Accuracy study. SETTING: University referral unit. PARTICIPANTS: 52 pregnant women with twin pregnancies and gestational age of between 24 and 34 weeks. MAIN MEASUREMENTS: Sensitivity, specificity, predictive values and relative risk ratios of the correlation between fetal fibronectin and preterm birth before 34 and 37 weeks using an immediate-reading membrane test on cervicovaginal secretions obtained from participants. RESULT: The sensitivity varied between 66.7% and 85.7%, whereas the specificity was from 58.3% to 81.8% according to gestational age at the time of sampling. The relative risk of spontaneous preterm birth after a positive fetal fibronectin test, as compared with a negative fetal fibronectin test, rose from 2.8 at 24-26 weeks to 4.1 at 27-30 weeks. Analyses of the risk of delivery before 34 weeks were not statistically significant. CONCLUSION: Fetal fibronectin in the cervicovaginal secretions of patients with twin pregnancies is a useful tool for the early identification of twin pregnancies likely to deliver before 37 weeks. However, the clinical value of the fibronectin test is limited because of low indices for prediction of delivery before 34 weeks. The best period for performing the fetal fibronectin test in twin pregnancies to predict preterm delivery is between 27 and 30 weeks.

Biomarkers↗

PubMed1999

Both protein kinase G dependent and independent mechanisms are involved in the modulation of glutamate release by nitric oxide in rat hippocampal nerve terminals.

We compared the effects of sodium nitroprusside (SNP), and of 8-bromo guanosine 3',5'-cyclic monophosphate (8-BrcGMP), on the 4-aminopyridine (4-AP)-evoked Ca2+-dependent release of glutamate from hippocampal nerve terminals and further investigated the role of protein kinase G (PKG) in this mechanism. SNP and 8-BrcGMP dose-dependently inhibited glutamate release, however SNP concentrations ([SNP]) > 500 microM abolished the 4-AP evoked release, whereas 8-BrcGMP maximally inhibited the release by about 30%. The inhibition of glutamate release at low concentrations of SNP (< or = 5 microM) was of about 20%, and was reversed by Rp-8(4-chlorophenylthio)guanosine-3',5'-cyclic-monophosphorotioate ) (RpCPTcGMP, 50 nM), but the inhibition at higher concentrations (5 < SNP < or = 50 microM) was insensitive to the PKG inhibitor, but sensitive to [1 H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one] (ODQ), which partially prevented the inhibition. [SNP] > 50 microM strongly inhibited glutamate release, and this was not reversed by either inhibitor. Furthermore, [SNP] < or = 50 microM enhanced cGMP formation, and the observed effects were not related to either decreased Ca2+ entry or ATP/ADP levels. Our results indicate that NO/PKG is the signaling pathway underlying the inhibition of glutamate release at low concentrations of NO, and imply that other NO-dependent, but PKG-independent, mechanisms are activated and have complementary roles at higher NO concentrations.

4-Aminopyridine↗

PubMed1999

Cutinase: from molecular level to bioprocess development.

This review analyzes the role of cutinases in nature and their potential biotechnological applications. The cloning and expression of a fungal cutinase, Fusarium solani f. pisi, in Escherichia coli and Saccharomyces cerevisiae hosts are described. The three-dimensional structure of this cutinase is also analyzed and its function as a lipase is discussed and compared with other lipases. The biocatalytic applications of cutinase are described taking into account the preparation of different cutinase forms and the media in which the different types of reactions have been performed, namely hydrolysis, esterification, transesterification, and resolution of racemic mixtures. The stability of cutinase preparations is discussed and, in particular, the cutinase stability in anionic reversed micelles is analyzed considering the role of hexanol as a substrate, a cosurfactant, and a stabilizer. Process development, based on the operation of cutinase reactors, is also reviewed.

Bioreactors↗

PubMed1999

Carbamazepine inhibits L-type Ca2+ channels in cultured rat hippocampal neurons stimulated with glutamate receptor agonists.

In order to better understand the mechanism(s) of action of carbamazepine (CBZ), we studied its effects on the increase in [Ca2+]i and [Na+]i stimulated by glutamate ionotropic receptor agonists, in cultured rat hippocampal neurons, as followed by indo- or SBFI fluorescence, respectively. CBZ inhibited the increase in [Ca2+]i stimulated either by glutamate, kainate, alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), or N-methyl-D-aspartate (NMDA), in a concentration-dependent manner. In order to discriminate the effects of CBZ on the activation of glutamate receptors from possible effects on Ca2+ channels, we determined the inhibitory effects of Ca2+ channel blockers on [Ca2+]i changes in the absence or in the presence of CBZ. The presence of 1 microM nitrendipine, 0.5 microM omega-conotoxin GVIA (omega-CgTx GVIA), or of both blockers, inhibited the kainate-stimulated increase in [Ca2+]i by 51.6, 32.9 or 68.7%, respectively. In the presence of both 100 microM CBZ and nitrendipine, the inhibition was similar (54.1%) to that obtained with nitrendipine alone, but in the presence of both CBZ and omega-CgTx GVIA, the inhibition was greater (54%) than that caused by omega-CgTx GVIA alone. However, CBZ did not inhibit the increase in [Na+]i stimulated by the glutamate receptor agonists, but inhibited the increase in [Na+]i due to veratridine. Tetrodotoxin, or MK-801, did not inhibit the influx of Na+ stimulated by kainate, indicating that Na+ influx occurs mainly through the glutamate ionotropic non-NMDA receptors. Moreover, LY 303070, a specific AMPA receptor antagonist, inhibited the [Na+]i response to kainate or AMPA by about 70 or 80%, respectively, suggesting that AMPA receptors are mainly involved. Taken together, the results suggest that CBZ inhibits L-type Ca2+ channels and Na+ channels, but does not inhibit activation of glutamate ionotropic receptors.

Animals↗