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Biomedical subjects

C Jacquot

Publications and source records attributed to C Jacquot.

At least 19 recordsLinked to original sources
PubMed2006

Membranous nephropathy and cancer: Epidemiologic evidence and determinants of high-risk cancer association.

The association between membranous nephropathy (MN) and cancer is often mentioned in textbooks but poorly substantiated, and the characteristics of cancer-associated MN are unknown. To address these questions, we studied a cohort of 240 patients with MN, among them 24 had malignancy at the time of renal biopsy or within a year thereafter. The incidence of cancer was significantly higher in these patients than in the general population (standardized incidence ratio 9.8 [5.5-16.2] for men and 12.3 [4.5-26.9] for women). The frequency of malignancy increased with age. At the time of diagnosis, clinical presentation did not differ between the patients with cancer-associated MN and those with idiopathic MN, but smoking was more frequent among patients with cancer. Analysis of renal biopsies revealed that the number of inflammatory cells infiltrating the glomeruli was significantly higher in patients with cancer-associated MN (P = 0.001). The best cutoff value for distinguishing malignancy-related cases from controls was eight cells per glomerulus. Using this threshold led to a diagnosis of cancer-associated MN with a specificity of 75% and a sensitivity of 92%. In patients with cancer-associated MN, there was a strong relationship between reduction of proteinuria and clinical remission of cancer (P < 0.001). In conclusion, our study provides epidemiologic evidence of an excess of cancer risk in patients with MN. It also shows that age, smoking, and the presence of glomerular leukocytic infiltrates strongly increase the likelihood of malignancy in MN patients.

Adult↗
PubMed2006

Acute oxalate nephropathy: A new etiology for acute renal failure following nonrenal solid organ transplantation.

Acute renal insufficiency (ARI) is a frequent complication of nonrenal solid organ transplantation and may be responsible for an unfavorable outcome, particularly if dialysis is required. The etiology of post-transplantation ARI is poorly understood, with only isolated clinical cases being reported, most imputed to drug toxicity. We report here, the first three observations of irreversible ARI associated with acute oxalate nephropathy (AON) in the course of nonrenal organ transplants: a lung transplant and a lung-liver transplant in two patients with mucoviscidosis, and a cardiac transplant. The diagnosis of AON was made histologically. In all three cases, the ARI supervened after prolonged consumption of antibiotics capable of interfering with the colonic flora, and leading to enteric hyperoxaluria. The recognition of AON as a cause of post-transplantation, ARI underlines hyperoxaluria and digestive hyperabsorption of oxalate as specific risk factors for AON and should permit better posttransplant care of these patients.

Acute Kidney Injury↗
PubMed2006

Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

Adult↗
PubMed2006

Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension.

A morphometric study was performed on 22 renal biopsies from hypertensive patients with proteinuria and/or azotemia, with no evidence of other renal disease. These results were compared with our earlier study of normotensive aging kidneys. Afferent arterioles in hypertensive kidneys showed a significant increase in lumen diameter (15.7+/-4.9 vs 13.4+/-4.7 microm, P=0.0007) and wall area (1234+/-769 vs 998+/-445 microm(2), P=0.037), due primarily to shift in the distribution of arteriolar types, from predominantly normal toward predominantly hyaline arterioles in hypertension. Glomeruli were divided into four basic types: normal, hypertrophic, focal segmental glomerulosclerosis (FSGS) type, and sclerosing. Overall, glomeruli in hypertensive kidneys were much larger than in normotensive aging kidneys, for example, total capillary area (16 247+/-10 681 vs 11 624+/-5702 microm(2), P<0.00001). This increase was due primarily to an increase in size of each type, for example, for hypertrophic glomeruli: total capillary area (22 205+/-10 426 vs 15 349+/-4577 microm(2), P=0.0038). There was an excellent correlation between arteriolar lumen diameter and mean glomerular capillary area for hypertrophic/FSGS-type glomeruli (r=0.4778, P=0.0013), such that as arteriolar diameter increases the mean glomerular capillary area increases, consistent with loss of autoregulation. The morphologic correlates of loss of autoregulation, with afferent arteriolar dilatation and increase in glomerular capillary size, glomerular hypertrophy, and subsequent FSGS, are present on a focal basis in aging kidneys and, much more extensively, although still focally, in hypertensive kidneys.

Adult↗
PubMed2004

Brown tumor of the spine and progressive paraplegia in a hemodialysis patient.

STUDY DESIGN: Case report. OBJECTIVE: To describe the radiographic features and management of spinal brown tumor and to document tumor mineralization after parathyroidectomy. SUMMARY OF BACKGROUND DATA: Brown tumors are classic skeletal manifestations of hyperparathyroidism usually seen in severe forms. They are increasingly rare because hyperparathyroidism is now diagnosed and treated at an early stage. METHODS: A case of brown tumor of the spine in a 37-year-old woman on chronic hemodialysis is described. The imaging findings before and after parathyroidectomy are discussed. RESULTS: In a woman on chronic hemodialysis, a brown tumor of T8 caused acute spinal cord compression with paraplegia. Magnetic resonance imaging provided an accurate evaluation of the lesion, and needle biopsy confirmed the diagnosis. Emergent surgery was needed to relieve the spinal compression and stabilize the spine. The vertebral lesion underwent remineralization after parathyroidectomy. CONCLUSION: Brown tumor is a benign tumor that resolves after parathyroidectomy. When brown tumor arises in the spine, surgery may be needed to preserve neurologic function.

Adult↗
PubMed2003

Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout mice.

The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, approximately 20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 micro m paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in the medial prefrontal cortex and ventral hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and the extraction fraction of 5-HT were similar in the medial prefrontal cortex and ventral hippocampus of both genotypes, suggesting that no compensatory response to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT uptake capacity occurred in vivo. As steady-state brain concentrations of paroxetine at day 14 were similar in both genotypes, it is unlikely that differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are due to alterations of the drug's pharmacokinetic properties in mutants. These data suggest that there are differences between the ventral hippocampus and medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their role in regulating dialysate 5-HT levels. These presynaptic receptors retain their capacity to limit 5-HT release mainly in the ventral hippocampus following chronic paroxetine treatment in mice.

Animals↗
PubMed2002

Foraging behavioural changes induced by conspecific and heterosubspecific odours in two strains of wild mice.

Mice in wild populations of the two subspecies Mus musculus domesticus and Mus musculus musculus may potentially compete for food. Because of the importance of olfaction in mice, we hypothesised that the presence of unfamiliar conspecific or heterosubspecific chemical cues could play a role in access to and use of food resources. We used an experimental design that tested this assumption with males from two strains, originated from wild populations of these subspecies, as subjects. Exploratory activity, latency of food approach, time and frequency on the food area, number of seeds eaten and foraging rate (number of seeds eaten/time on the food areax100) were compared for three different categories of odours (own, same strain and other strain odours) in both strains. In a foraging context, unfamiliar odours induced behavioural changes in male mice, especially an increase in exploratory activity from the more (same strain) to the less similar odour (different strain), and a reduction of time spent in the food area. Odour similarity related to genetic proximity in Mus and the cost-benefit ratio of an encounter are two possible explanations for the different processes involved in the treatment of odours in these two strains of mice.

Journal Article↗
PubMed2001

5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization.

Antagonists at substance P receptors of the neurokinin 1 (NK1) type have been shown to represent a novel class of antidepressant drugs, with comparable clinical efficacy to the selective serotonin (5-HT) reuptake inhibitors (SSRIs). Because 5-HT(1A) receptors may be critically involved in the mechanisms of action of SSRIs, we examined whether these receptors could also be affected in a model of whole-life blockade of NK1 receptors, i.e. knock-out mice lacking the latter receptors (NK1-/-). 5-HT(1A) receptor labeling by the selective antagonist radioligand [(3)H]N-[2-[4-(2-methoxyphenyl)1-piperazinyl]-ethyl]-N-(2-pyridinyl)-cyclohexanecarboxamide (WAY 100635) and 5-HT(1A)-dependent [(35)S]GTP-gamma-S binding at the level of the dorsal raphe nucleus (DRN) in brain sections, as well as the concentration of 5-HT(1A) mRNA in the anterior raphe area were significantly reduced (-19 to -46%) in NK1-/- compared with NK1+/+ mice. Furthermore, a approximately 10-fold decrease in the potency of the 5-HT(1A) receptor agonist ipsapirone to inhibit the discharge of serotoninergic neurons in the dorsal raphe nucleus within brainstem slices, and reduced hypothermic response to 8-OH-DPAT, were noted in NK1-/- versus NK1+/+ mice. On the other hand, cortical 5-HT overflow caused by systemic injection of the SSRI paroxetine was four- to sixfold higher in freely moving NK1-/- mutants than in wild-type NK1+/+ mice. Accordingly, the constitutive lack of NK1 receptors appears to be associated with a downregulation/functional desensitization of 5-HT(1A) autoreceptors resembling that induced by chronic treatment with SSRI antidepressants. Double immunocytochemical labeling experiments suggest that such a heteroregulation of 5-HT(1A) autoreceptors in NK1-/- mutants does not reflect the existence of direct NK1-5-HT(1A) receptor interactions in normal mice.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Interaction between 5-HT(1A) and 5-HT(1B) receptors: effects of 8-OH-DPAT-induced hypothermia in 5-HT(1B) receptor knockout mice.

To test for adaptive compensatory changes that may have occurred in the functional activity of somatodendritic 5-HT(1A) receptors during the development of constitutive "knockout" mice lacking the 5-HT(1B) receptor subtype (5-HT(1B) -/- KO), we assayed for decrease in body temperature induced by an acute subcutaneous injection of the 5-HT(1A) receptor agonist, 8-hydroxy 2(di-n-propyl(amino)tetralin (8-OH-DPAT), either alone or in the presence of a selective 5-HT(1A) receptor antagonist, N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide (WAY 100635). We compared dose-response curves, time course study, calculated ED(50) values (potency), maximal response to 8-OH-DPAT (efficacy) as well as measurements of the dose-dependent blockade of this response by WAY 100635 between wild-type controls and mutant mice. We found a higher efficacy of 8-OH-DPAT-induced hypothermia in 5-HT(1B) -/- KO compared to wild-type mice suggesting that an adaptive thermoregulatory process involving the functional activity of somatodendritic 5-HT(1A) receptors is altered in mutant mice lacking 5-HT(1B) receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Up-regulation of a novel mRNA (NY-CO-1) involved in the methyl 4-methoxy-3-(3-methyl-2-butenoyl) benzoate (VT1)-induced proliferation arrest of a non-small-cell lung carcinoma cell line (NSCLC-N6).

It is now well known that treatment of tumors, especially non-small-cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. In this regard, our work is about genetic modifications arising in an in vitro NSCLC cell line after treatment with a chemical substance, methyl 4-methoxy-3-(3-methyl-2-butenoyl) benzoate (VT1). First, we showed that VT1 induces arrest of proliferation by blocking cells in the G1 phase of the cell cycle. Second, we use "differential display" strategy to clarify the genetic mechanisms involved in this proliferation arrest. A novel mRNA, NY-CO-1 (New-York Colon 1), of unknown function showed up-regulated expression after treatment. Application of "antisense" strategy confirmed this novel mRNA induction was effectively linked to growth arrest. Therefore, these data provide new information about mechanisms participating in arrest of proliferation of tumor cells and open new ways of treatment to target tumor growth.

Alkenes↗
PubMed2001

[5-HT1B serotonin receptors and antidepressant effects of selective serotonin reuptake inhibitors ].

We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 5-HT1B receptor subtype in mediating the effects of selective serotonin reuptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg dose but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiates the effect of a single administration of paroxetine on [5-HT]ext more in the ventral hippocampus than in the frontal cortex. Furthermore, we demonstrate that SSRIs decrease immobility in the forced swimming test; this effect is absent in 5-HT1B knockout mice and blocked by GR 127935 in wild-type suggesting therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these data demonstrate that 5-HT1B autoreceptors appear to limit the effects of SSRI on dialysate 5-HT levels particularly in the hippocampus while presynaptic 5-HT1B heteroreceptors are likely to be required for the antidepressant activity of SSRIs.

Animals↗
PubMed2001

5-HT1B Autoreceptors limit the effects of selective serotonin re-uptake inhibitors in mouse hippocampus and frontal cortex.

We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 1B receptor subtype in mediating the effects of selective serotonin re-uptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg, but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiated the effect of a single administration of paroxetine on extracellular 5-HT levels more in the ventral hippocampus than in the frontal cortex. These data suggest that 5-HT1B autoreceptors limit the effects of SSRIs on dialysate 5-HT levels at serotonergic nerve terminals.

Animals↗
PubMed2001

Factors associated with increased serum levels of cardiac troponins T and I in chronic haemodialysis patients: Chronic Haemodialysis And New Cardiac Markers Evaluation (CHANCE) study.

BACKGROUND: Serum concentrations of the cardiac troponins (cTn) T and I, specific markers of myocardial injury, are frequently elevated in haemodialysis patients. The clinical relevance of this is unclear. The aim of this study was to investigate factors associated with increased serum levels of cTn in haemodialysis patients. METHODS: We included in this cross-sectional study 258 chronic haemodialysis patients (150 men, age 60+/-15 years) without acute coronary symptoms. Clinical data, echocardiographic hypertrophy, biochemical status, and haemodialysis regimen were evaluated for each patient. Pre-dialysis serum cTnT (Elecsys, Roche), cTnI (Stratus and RXL, Dade-Berhing), and CK-MB (Stratus, Dade-Berhing) concentrations were determined. Logistic regression was the principal method of analysis. RESULTS: Pre-dialysis levels of cTnT >0.1 ng/ml (n=48, 18.6% of patients) were associated with age (P<0.001), diabetes (P<0.005), history of ischaemic heart disease (P<0.05), and left ventricular hypertrophy (P<0.05). In multivariate analysis, age odds ratio ((OR) 1.04), diabetes (OR 4.9), and indexed left ventricular mass (OR 1.01) were found to be independently associated with cTnT concentration above the threshold. Only six patients had cTnI-Stratus levels >0.6 ng/ml. cTnI-RXL levels >0.3 ng/ml (n=13, 5.0%) were associated with age (P=0.05) and hypercholesterolaemia (P<0.05). Only age (OR 1.06) remained associated in multivariate analysis. CONCLUSION: Elevated baseline serum levels of cardiac troponins were associated with cardiovascular risk factors, history of ischaemic heart disease and left ventricular hypertrophy in asymptomatic chronic haemodialysis patients.

Adolescent↗
PubMed2001

Assessing pain in critically ill sedated patients by using a behavioral pain scale.

OBJECTIVE: To establish the validity and reliability of a new behavioral pain scale (BPS) for critically ill sedated adult patients. DESIGN: Prospective evaluation. SETTING: Ten-bed trauma and surgical intensive care unit in a university teaching hospital. PATIENTS: Thirty mechanically ventilated patients who were receiving analgesia and sedation. INTERVENTION: Assessments with the BPS were completed consecutively at standardized times (morning, afternoon, night) by pairs of evaluators (nurse and nurse's aide). They collected physiologic parameters and BPS results before and during care procedures: non-nociceptive (group 1, compression stockings application and central venous catheter dressing change), nociceptive (group 2, endotracheal suctioning and mobilization), and retested nociceptive (group 3). The BPS score was the sum of three items that had a range score of 1-4: facial expression, movements of upper limbs, and compliance with mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Two hundred and sixty nine assessments were completed, including 104, 134, and 31 measurements in groups 1, 2 and 3, respectively. There was no difference in Ramsay scale scores between the three groups (Ramsay 4-6). Nociceptive stimulations (group 2) resulted in significantly higher BPS values than non-nociceptive ones (group 1, 4.9 vs. 3.5, p <.01), whereas the two groups had comparable BPS values before stimulation (3.1 vs. 3.0). A trend was found in group 2 between the dosage of sedation/analgesia and BPS: the higher the dosage, the lower BPS values and BPS changes to nociceptive stimulation. Group 3 had BPS values similar to group 2 at rest (3.2 vs. 3.2) and during the procedure (4.4 vs. 4.5), with good interrater correlations (r(2) =.71 and.50, respectively). CONCLUSIONS: These results indicate that the expression of pain can be scored validly and reliably by using the BPS in sedated, mechanically ventilated patients. Further studies are warranted regarding the utility of the BPS in making clinical decisions about the use of analgesic drugs in the intensive care unit.

Adult↗
PubMed2001

Cholesterol crystal embolization demonstrated on GI biopsy.

OBJECTIVES: Cholesterol crystal embolism is a severe complication of atherosclerosis responsible for nonspecific cutaneous, renal, and, less often, digestive manifestations that may mimic other systemic diseases. METHODS: We reviewed retrospectively 10 patients with histologically proven cholesterol crystal emboli diagnosed by endoscopic GI biopsy. RESULTS: All patients had prior clinical manifestations of severe atherosclerosis and predisposing factors for cholesterol migration. They all had cutaneous manifestations of cholesterol crystal embolism, acute renal failure, and biological inflammatory syndrome. Digestive symptoms were found in the 10 patients: abdominal pain in eight, diarrhea in four, and GI bleeding in three. GI endoscopy ruled out specific digestive diseases, showing only a congestive or erosive mucosa. Histological diagnosis of cholesterol crystal emboli was based on gastric biopsy in nine patients, duodenal biopsy in four, colonic biopsy in three, and rectal biopsy in one, with six having positive biopsies on multiple sites. Outcome after the diagnosis of cholesterol crystal embolism was poor, with all patients requiring permanent hemodialysis. Death by atherosclerosis complications occurred in five patients. CONCLUSIONS: This cohort suggests that upper GI endoscopy may be helpful in demonstrating the presence of cholesterol crystal embolism, and that diagnosis of cholesterol crystal emboli on digestive tract biopsy indicates advanced systemic atherosclerosis disease of poor prognosis.

Acute Kidney Injury↗
PubMed1999

Simultaneous effects of local dexfenfluramine application on extracellular glutamate and serotonin levels in rat frontal cortex: a reverse microdialysis study.

We examined the effects of local perfusion by reverse dialysis of various doses of dexfenfluramine (D-fen; in mM: 2.4, 12, and 24) simultaneously on serotonin (5-HT; [5-HT]ext) and glutamate (Glu; [Glu]ext) extracellular levels in the frontal cortex of awake rats. D-fen induced a dose-dependent increase in both [5-HT]ext and [Glu]ext, the latter being Ca2+ -dependent and TTX-sensitive, while the former is not. Pretreatment with either the neurotoxin p-chloroamphetamine or the 5-HT uptake blocker fluoxetine, markedly reduced the effects of D-fen on [5-HT]ext and [Glu]ext compared to controls. This indicates that intact 5-HT nerve terminals may be required for D-fen to enter into neurones to release 5-HT by reversal of the 5-HT transporter, which then increases frontocortical [Glu]ext. Pretreatment with the Glu uptake blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM), significantly reduced by 40% the effect of D-fen's on [Glu]ext suggesting that Glu uptake sites are partially involved in this effect. These results strongly suggest that intracortical application, by reverse dialysis, of a high dose of D-fen increases frontocortical [Glu]ext by a dual mechanism of action: (1) by stimulating 5-HT release (a major indirect effect) that, in turn, facilitates the release of neuronal Glu; (2) by reversal of the glutamate transporter (a minor direct effect being Ca2+ -independent and TTX-insensitive).

Animals↗