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Biomedical subjects

C Thomsen

Publications and source records attributed to C Thomsen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Autoradiographic visualization of group III metabotropic glutamate receptors using [3H]-L-2-amino-4-phosphonobutyrate.

1. In vitro receptor autoradiography using [3H]-L-2-amino-4-phosphonobutyrate ([3H]-L-AP4) binding to sections of rat brain has been characterized and shown to most likely represent labelling of group III metabotropic glutamate receptors. 2. Specific [3H]-L-AP4 binding to rat brain sections was observed at high densities in the molecular layer of the cerebellar cortex and the outer layer of the superior colliculus. Moderate levels were observed throughout the cerebral cortex, in the molecular layer of the hippocampal dentate gyrus, in thalamus, striatum, substantia nigra and in the medial geniculate nucleus. Low levels of [3H]-L-AP4 binding were found in other regions of the hippocampal formation, in the entorhinal cortex and the granule cell layer of cerebellum. 3. Inhibitors of sodium- or calcium/chloride-dependent glutamate uptake did not displace [3H]-L-AP4 binding to rat brain sections indicating that the observed binding does not represent [3H]-L-AP4 uptake via these carriers. Furthermore, in contrast to [3H]-L-AP4 uptake into cerebellar membranes, [3H]-L-AP4 binding to brain sections was sensitive to guanosine-5'-O-(3-thio)trisphosphate-gamma-S. 4. In the molecular layer of the cerebellar cortex, [3H]-L-AP4 binding showed a maximal binding density (Bmax) of 0.52+/-0.06 pmol mg(-1) tissue and an affinity (Kd) of 346 nM. The rank order of affinity for displacement of [3H]-L-AP4 binding to rat brain sections was: L-AP4 > L-serine-O-phosphate > glutamate > (L)-2-aminomethyl-4-phosphonobutanoate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate which is in agreement with a group III metabotropic glutamate receptor pharmacology.

Aminobutyrates↗
PubMed1998

von Willebrand factor (vWf) as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:AgII).

Elevated plasma von Willebrand factor (vWf) levels are found in diabetes and other vasculopathies, and predict cardiovascular mortality. vWf is stored and released from endothelial cell secretory granules, along with equimolar amounts of its propeptide (vWf:AgII). In the present study, we examined plasma propeptide levels as a marker of endothelial secretion in vivo, using an ELISA based on monoclonal antibodies. vWf but not propeptide levels are influenced by blood groups, explaining in part the smaller variation in plasma propeptide levels among normal individuals. In both controls and insulin-dependent diabetic patients, we found a close correlation between propeptide and immunoreactive vWf levels (r2=0.54, p <0.0001). vWf and propeptide were elevated in patient subgroups with microalbuminuria or overt diabetic nephropathy, whereas only the propeptide was significantly elevated in the normoalbuminuric subgroup. This observation suggests that in conjunction with vWf, propeptide measurements may improve the identification of endothelial activation, which occurs frequently even without increased urinary albumin excretion. In 12 NIDDM patients, a 3-week diet enriched in monounsaturated fat (MUFA) resulted in parallel decreases in vWf (-22%, p <0.05) and propeptide (-17%, p <0.05) levels, indicating that the experimental diet affected endothelial secretion rather than vWf catabolism. A carbohydrate-enriched control diet did not significantly influence either marker. Our results suggest that concomitant determinations of plasma vWf and propeptide are useful tools to assess endothelial activation in vivo, and reinforce our previous conclusion that a diet rich in MUFA can improve endothelial function in NIDDM.

Adult↗
PubMed1997

MR diffusion imaging of human intracranial tumours.

We used MRI for in vivo measurement of brain water self-diffusion in patients with intracranial tumours. The study included 28 patients (12 with high-grade and 3 with low-grade gliomas, 7 with metastases, 5 with meningiomas and 1 with a cerebral abscess). Apparent diffusion coefficients (ADC) were calculated in a single axial slice through the tumours, the sequence was sensitive to diffusion along the cephalocaudal axis. Our main finding was that ADC in contrast-enhancing areas within cerebral metastases was statistically significantly higher than ADC in contrast-enhancing areas in high-grade gliomas (P < or = 0.05). Furthermore, the ADC in oedema surrounding metastases were statistically significantly higher the ADC in oedema around high-grade gliomas (P < or = 0.02). The ADC in patients with meningiomas did not differ significantly from those seen with high-grade gliomas or cerebral metastases. The highest ADC were found within cystic or necrotic tumour areas. In one patient with a cerebral abscess, suspected of having a high-grade glioma, the ADC was similar to that in high-grade gliomas. The finding of higher ADC in cerebral metastases than in high-grade gliomas may be helpful in trying to distinguish between these tumours preoperatively; it suggests increased free extracellular and/or intracellular water fraction in cerebral metastases. The method seems to hold potential for further noninvasive characterisation of intracranial tumours.

Adult↗
PubMed1997

The day-to-day variation in insulin sensitivity in non-insulin-dependent diabetes mellitus patients assessed by the hyperinsulinemic-euglycemic clamp method.

The objective was to study the day-to-day variation in insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) and to analyze within- and between-person variances in the glucose infusion rate during steady state (M value). Ten NIDDM patients attending the outpatient clinic at Aarhus Amtssygehus were studied three times under standardized conditions. Each time, a 120-minute hyperinsulinemic-euglycemic clamp was performed. Similar M values were found on the 3 study days, with difference between M values on the 3 days of (mean +/- SD) 0.3 +/- 1.8 mg glucose/kg lean body mass (LBM)/min. The total coefficient of variation (CV) for M values was 57% after the first clamp, 55% after the second, and 53% after the third. Ninety percent of the total day-to-day variation in M values could be ascribed to between-person variation and 10% to within-person variation. Within-person components of variance included all sources of variation other than between-person variation. The within-person CV for M values was 11.9% +/- 7.2% after two clamp studies and 12.1% +/- 7.3% after three (P < .55). In conclusion, under standardized conditions, a valid estimate of insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp in NIDDM patients is obtained after a single measurement. Because of large between-person variation, paired data should be used when comparing insulin sensitivity in NIDDM patients.

Blood Glucose↗
PubMed1997

Cloning and characterization of a metabotropic glutamate receptor, mGluR4b.

An alternative spliced variant of metabotropic glutamate receptor subtype mGluR4a, termed mGluR4b was isolated from a rat cDNA library. Subtype mGluR4b was identical to the previously described mGluR4a, except for the last 64 amino acids in the C-terminal region in which were replaced by 135 new amino acids in mGluR4b. Recombinant baculoviruses coding for mGluR4a and mGluR4b were expressed in Spodoptera frugiperda, Sf-9, insect cells and characterized pharmacologically by measuring [3H]-L-2-amino-4-phosphonobutyrate ([3H]-L-AP4) binding and second messenger formation. [3H]-L-AP4 binding to membranes prepared from Sf-9 cells expressing mGluR4a and mGluR4b revealed respective affinities (Kd) of 480 and 360 nM and maximal binding densities (Bmax) of 4.2 and 0.8 pmol/mg protein. The ligand selectivity of mGluR4a and mGluR4b was similar: L-AP4 > L-serine-O-phosphate > L-glutamate > L-2-amino 2-methyl-4-phosphonobutyrate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate > or = quisqualate. A decrease in the affinity of [3H]-L-AP4 was observed in the presence of 0.1 mM guanosine 5'-O-(3-thio)trisphosphate-gamma-S, indicating that mGluR4a and mGluR4b were functionally coupled to G-proteins in Sf-9 cells. Agonists of mGluR4 caused a minor decrease in forskolin-induced cAMP formation in Sf-9 cells expressing either mGluR4a or mGluR4b, suggesting that both receptors are coupled to adenylate cyclase in an inhibitory manner. Thus, mGluR4a and mGluR4b share a common signal transduction pathway and pharmacology when expressed in Sf-9 insect cells.

Amino Acid Sequence↗
PubMed1997

The L-AP4 receptor.

1. The L-2-amino-4-phosphonobutyric acid (L-AP4) receptor was originally discovered by the ability of L-AP4 to depress synaptic transmission in hippocampal glutamatergic pathways and in the retina. 2. The molecular identity of the L-AP4 receptor is not yet resolved; however, with the molecular cloning of subtypes of metabotropic glutamate receptors (mGluRs), high affinity targets for L-AP4 have been identified. 3. As the information on the pharmacology of the mGluRs and the electrophysiological and biochemical studies on L-AP4 receptor physiology becomes elaborated it seems evident that the L-AP4 receptor is not a single molecular target but may involve multiple receptor subtypes.

Animals↗
PubMed1997

Quantification of low-velocity motion using a navigator-echo supported MR velocity-mapping technique: application to intracranial dynamics in volunteers and patients with brain tumours.

Gradient-echo pulse sequences with velocity-encoding gradients of 22.5-25 mT/m, were used for brain-motion and CSF-flow studies. To reduce motion artifacts, a phase-correction technique based on navigator echoes was evaluated. Three patients with right-sided parietal tumours were investigated; one astrocytoma grade III-IV, one astrocytoma grade I-II and one benign meningioma. In healthy volunteers, a maximal brain-tissue velocity of (0.94 +/- 0.26) mm/s (mean +/- 1SD) was observed, which is consistent with previously presented results. The phase correction was proven useful for reduction of artifacts due to external head movements in modulus and phase images, without loss of phase information related to internal motion. The tissue velocity within the astrocytomas was low during the entire cardiac cycle. An abnormally high rostral velocity component was, however, observed in the brain tissue frontal to the astrocytomas. In all patients, an abnormal CSF flow pattern was observed. The study of brain motion may provide further understanding of the effects of tumours and other pathological conditions in the brain. When considering intracranial motion as a source of error in diffusion/perfusion MRI, the present study suggests that a pathology can alter the properties of brain motion and CSF flow considerably, leading to a more complex impact on diffusion/perfusion images.

Adult↗
PubMed1997

Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05-2090, not acting preferentially on GAT-1.

Two novel nipecotic acid derivatives, 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(4-methoxyphenyl)-4-piperidino l (NNC 05-2045) and 1-(3-(9H-Carbazol-9-yl)-l-propyl)-4-(2-methoxyphenyl)-4-piperidino l (NNC 05-2090) have been tested for inhibition of gamma-amino butyric acid (GABA) transporters in synaptosomal preparations of rat cerebral cortex and inferior colliculus and found to differ markedly from gabitril (tiagabine), a selective GAT-1 inhibitor. IC50 values for inhibition of [3H]GABA uptake into synaptosomes from cerebral cortex for NNC 05-2045 and NNC 05-2090 were 12 +/- 2 and 4.4 +/- 0.8 microM, respectively. In synaptosomes from inferior colliculus in the presence of 1 microM 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid (NNC 05-0711), a highly potent and selective GAT-1 inhibitor, IC50 values for inhibition of [3H]GABA uptake were 1.0 +/- 0.1 and 2.5 +/- 0.7 microM, respectively. A receptor profile showed that NNC 05-2045 has binding affinities to sigma-, alpha 1- and D2-receptors of 113, 550 and 122 nM, respectively. NNC 05-2090 displayed alpha 1- and D2-receptor affinity of 266 and 1632 nM, respectively. The anticonvulsant action of both compounds was tested in four rodent models after intra peritoneal (i.p.) injection. Both NNC 05-2090 dose-dependently inhibited sound-induced tonic and clonic convulsions in DBA/2 mice with ED50 values of 6 and 19 mumol/kg, respectively. NNC 05-2045 also antagonized sound-induced seizures in genetic epilepsy prone rats (GEP rats) with ED50 values against wild running, clonic and tonic convulsions of 33, 39 and 39 mumol/kg, respectively (NNC 05-2090 was not tested in GEP rats). Both NNC 05-2045 and NNC 05-2090 dose-dependently antagonized tonic hindlimb extension in the maximal electroshock (MES) test with ED50 values of 29 and 73 mumol/kg, respectively. In amygdala kindled rats NNC 05-2045 and NNC 05-2090 significantly (P < 0.05) reduced generalized seizure severity (seizure grade 3-5) at highest doses (72-242 mumol/kg) and NNC 05-2090 also significantly reduced afterdischarge duration at these doses (P < 0.05). These data show that inhibition of GABA uptake through non-GAT-1 transporters has different anticonvulsant effects than selective GAT-1 inhibitors (e.g. tiagabine) in that enhanced efficacy against MES and reduced efficacy against kindled seizures is observed. Although a contribution of adrenergic agonistic effects cannot be entirely ruled out, it is proposed that inhibition of GAT-3 (mouse GAT4) is primarily responsible for the anticonvulsant action of these two nipecotic acid derivatives in MES, amygdala kindled rats and in sound-induced seizures in GEP-rats and DBA/2 mice.

Animals↗
PubMed1997

Nutritional support in advanced pulmonary disease.

Advanced pulmonary disease (APD), often secondary to emphysema or chronic bronchitis, is generally a progressive, incurable condition, ultimately leading to death. The condition is associated with significant, distressing symptoms. Most APD patients are underweight, which has numerous implications including accentuation of reduced physical capacity during daily life, increased risk of other secondary diseases, e.g. infections and osteoporosis, and a higher mortality during exacerbations with acute respiratory failure. Consequently, careful nutritional support is crucial both in enhancing physical well-being and function, and in reducing the risk of acute respiratory failure. Knowledge concerning the exact nutritional needs in APD is still very sparse; however, specific actions against malnutrition in APD patients should be mandatory in the treatment of APD. This paper reviews the literature concerning implications of malnutrition and benefits of nutritional support in APD patients, and gives suggestions for the practical, daily-life nutritional management of APD.

Chronic Disease↗
PubMed1997

1-(3-(9H-carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidinol, a novel subtype selective inhibitor of the mouse type II GABA-transporter.

The selectivity of new derivatives of the gamma-aminobutyric acid (GABA)-uptake inhibitor, tiagabine was characterized at the four cloned mouse GABA transporters (mGAT1 through mGAT4) by measuring [3H]-GABA uptake into stably transfected baby hamster kidney cells. While tiagabine is a highly selective inhibitor of mGAT1 (Ki = 0.11 +/- 0.02 microM), these derivatives exhibited low potencies at mGAT1 but differential activities at mGAT2, mGAT3 and mGAT4. In particular, 1-(3-(9H-carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidino l (NNC 05-2090) was a potent inhibitor of mGAT2 (Ki = 1.4 +/- 0.3 microM) showing at least 10 fold selectivity over mGAT1, mGAT3 and mGAT4. NNC 05-2090 is the first subtype selective inhibitor of mGAT2 and may represent a novel useful tool for investigating the physiological roles of GAT2 in the brain and periphery.

Animals↗
PubMed1997

The perfusion fraction in volunteers and in patients with ischaemic stroke.

The fractional volume of capillary blood, i.e. the perfusion fraction f, was measured with the aid of an echo-planar imaging protocol originally designed for the measurement of water diffusion. In healthy volunteers, reasonable f values were obtained. In patients with cerebral ischaemic stroke, a marked decrease in the f value was seen in the infarcted region as compared with corresponding values in the contralateral hemisphere. We suggest that perfusion-fraction measurements may add to the diagnostic value of water-mobility examinations in patients with ischaemic disease.

Adult↗
PubMed1997

Enhanced type 1alpha metabotropic glutamate receptor-stimulated phosphoinositide signaling after pertussis toxin treatment.

The regulation of phosphoinositide hydrolysis by the type 1alpha metabotropic glutamate receptor (mGluR1alpha) was investigated in stably transfected baby hamster kidney (BHK) cells. Incubation of the cells with L-glutamate, quisqualate, and 1-aminocyclopentane-1S, 3R-dicarboxylic acid resulted in a marked accumulation of [3H]inositol monophosphate (InsP1) and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] mass in a time- and concentration-dependent manner. Pretreatment of BHK-mGluR1alpha cells with pertussis toxin [ 100 ng/ml, 24 hr] led to a dramatic 12-16-fold increase in the accumulation of [3H]InsP1 and a 2-fold increase in Ins(1,4,5)P3 in the absence of added agonist. Although only very low levels (</=1 microM) of L-glutamate could be detected in medium taken from control and PTX-treated cell monolayers, the PTX-elicited effect on basal [3H]InsP1 was fully reversed by preincubation of cells in the presence of glutamic-pyruvic transaminase and pyruvate, suggesting that an increased sensitivity to endogenous glutamate was responsible for the apparent agonist-independent activation of phosphoinositidase C (PIC) after PTX treatment. Consistent with this hypothesis, in the presence of glutamic-pyruvic transaminase/pyruvate, the maximal [3H]InsP1 response to quisqualate was increased by >/=75%, and the EC50 shifted leftward by 65-fold [-log EC50 values (molar), 7.26 +/- 0.23 versus 5.45 +/- 0.07; n = 4) in PTX-treated compared with control cells. In contrast, antagonist effects on agonist-stimulated [3H]InsP1 responses were similar in control and PTX-treated BHK-mGluR1alpha cells. These changes in the concentration-effect curves for mGluR agonists are consistent with a model in which the receptor associates with PTX-sensitive inhibitory (Gi/o) and PTX-insensitive stimulatory (Gq/11) G proteins that can each influence PIC activity. The present observations are consistent with a dual regulation of mGluR1alpha-mediated PIC activity that could be fundamental in controlling the output of phosphoinositide-derived messengers.

Amino Acid Sequence↗
PubMed1997

Comparison of the effects of two weeks' intervention with different meal frequencies on glucose metabolism, insulin sensitivity and lipid levels in non-insulin-dependent diabetic patients.

AIMS: To compare the effects of 2 weeks on different meal frequencies on glucose metabolism, lipid levels and 24-hour blood pressure in non-insulin-dependent diabetic subjects. METHODS: Ten non-insulin-dependent diabetic outpatients from Aarhus City participated in a crossover study design. None were treated with insulin. The patients were randomly allocated to two isoenergetic diets either taken as three or eight meals per day for 2 weeks each. At the end of each period, the diurnal blood pressure and the responses to a test meal were measured. Furthermore, a hyperinsulinemic, euglycemic clamp was placed. RESULTS: Both the insulin sensitivity and 24-hour ambulatory blood pressure were similar as were the responses of glucose, insulin and free fatty acids to a carbohydrate-rich test meal at the end of the two diet periods. The HDL-cholesterol level was lowest in response to the 8-meal diet (p = 0.02). CONCLUSION: Increasing meal frequencies in a 2-week treatment period with weight-maintaining diets on an outpatient basis subdued the HDL-cholesterol levels but apparently had no impact on glucose metabolism or diurnal blood pressure in NIDDM subjects. These results give no indications of long-term beneficial effects of increasing the meal frequency in NIDDM patients.

Blood Glucose↗
PubMed1997

Comparison of a carbohydrate-rich diet and diets rich in stearic or palmitic acid in NIDDM patients. Effects on lipids, glycemic control, and diurnal blood pressure.

OBJECTIVE: To compare the effects on lipid levels, glycemic control, and diurnal blood pressure of two diets rich in one of the two quantitatively most important saturated fatty acids, stearic and palmitic acid, with a carbohydrate-rich diet in NIDDM patients. RESEARCH DESIGN AND METHODS: A total of 15 NIDDM patients participated in a randomized crossover study with three 3-week diet interventions separated by 2-week washout periods. Patients started with a diet rich in stearic acid (44 E% [percent of total energy] fat [13 E% stearic acid], 40 E% carbohydrate, 15 E% protein), palmitic acid (45 E% fat [16 E% palmitic acid], 40 E% carbohydrate, 15 E% protein), or carbohydrate (29 E% fat, 51 E% carbohydrate, and 18 E% protein), then were shifted to the other two diets in a randomized block design. At the start and end of each intervention period, fasting blood samples were drawn for analysis of lipids and blood glucose. In addition, diurnal blood pressure was measured. RESULTS: At the end of the 3-week interventions, total cholesterol was significantly higher after the palmitic acid-rich diet than after the stearic acid-rich or carbohydrate-rich diets (5.3 +/- 1.3 vs. 5.0 +/- 1.2 and 4.9 +/- 1.2 mmol/l, respectively; P = 0.03). No significant differences in triglyceride, LDL, or HDL cholesterol levels were seen after the three intervention diets. No difference in effects between the diet periods were seen for fructosamine, HbA1c, fasting blood glucose, or diurnal blood pressure. CONCLUSIONS: For the first time, it has been demonstrated that a diet rich in palmitic acid was not as effective in lowering cholesterol levels as carbohydrate-rich and stearic acid-rich diets in NIDDM patients. No deleterious effects were seen on diurnal blood pressure, triglyceride levels, and glycemic control. Development of foods containing stearic acid rather than the more atherogenic saturated fatty acids may allow a wider choice of acceptable foods to NIDDM patients.

Adult↗
PubMed1997

Pharmacological characterization of 1-aminoindan-1,5-dicarboxylic acid, a potent mGluR1 antagonist.

We examined the pharmacological profile of 1-aminoindan-1,5-dicarboxylic acid (AIDA), a rigid (carboxyphenyl)glycine derivative acting on metabotropic glutamate receptors (mGluRs). In cells transfected with mGluR1a, AIDA competitively antagonized the stimulatory responses of glutamate and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] on phosphoinositide hydrolysis (pA2 = 4.21). In cells transfected with mGluR5a, AIDA displayed a much weaker antagonist effect. In transfected cells expressing mGluR2, AIDA (< or = 1 mM) did not affect the inhibition of forskolin-stimulated adenylate cyclase activity induced by (1S,3R)-ACPD, but at large concentrations, it displayed a modest agonist activity. In rat hippocampal or striatal slices, AIDA (0.1-1 mM) reduced the effects of (1S,3R)-ACPD on phospholipase C but not on adenylate cyclase responses, whereas (+)-alpha-methyl-4-carboxyphenylglycine (0.3-1 mM) was an antagonist on both transduction systems. In addition, AIDA (0.3-1 mM) had no effect on mGluRs coupled to phospholipase D, whereas (+)-alpha-methyl-4-carboxy-phenylglycine (0.5-1 mM) acted as an agonist with low intrinsic activity. In rat cortical slices, AIDA antagonized the stimulatory (mGluR1-mediated) effect of (1S,3R)-ACPD on the depolarization-induced outflow of D-[3H]aspartate, disclosing an inhibitory effect ascribable to (1S,3R)-ACPD activating mGluR2 and/or mGluR4. Finally, mice treated with AIDA (0.1-10 nmol i.c.v.) had an increased pain threshold and difficulties in initiating a normal ambulatory behavior. Taken together, these data suggest that AIDA is a potent, selective and competitive mGluR1 a antagonist.

Adenylyl Cyclases↗
PubMed1996

Synthesis and pharmacological characterization of all sixteen stereoisomers of 2-(2'-carboxy-3'-phenylcyclopropyl)glycine. Focus on (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a novel and selective group II metabotropic glutamate receptors antagonist.

All 16 2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCGs) stereoisomers 32-47 have been prepared from the corresponding racemic aldehydes 12-15 following an enantiodivergent synthetic protocol. Compounds 32-47 were evaluated by a number of binding and functional experiments as potential ligands for several classes of excitatory amino acid receptors, including metabotropic glutamate receptors (mGluR1a, mGluR2, mGluR4) and ionotropic glutamate receptors (NMDA, KA, AMPA) as well as sodium-dependent and calcium/ chloride-dependent glutamate transport systems. The stereolibrary of compounds 32-47 appears to be endowed with a peculiar pharmacological profile. PCCG-2 (33) and PCCG-3 (34) displaced labeled kainate at low micromolar concentration; PCCG-9 (40) and PCCG-11 (42) weakly interacted with the NMDA site; PCCG-5 (36), PCCG-10 (41), and PCCG-12 (43) showed to be potent inhibitors of Ca2+/Cl(-)-dependent glutamate transport system. Most interestingly, PCCG-4 (35) has been shown to be able to antagonize (IC50 = 8 microM) the effects of glutamate on forskolin-stimulated cAMP formation in BHK cells expressing mGluR2. Uneffective at mGluR1, 35 is a weak mGluR4 agonist (EC50 = 156 microM) and has no effect on either ionotropic receptors or glutamate transport systems, thus demonstrating to be a novel selective mGluR2 antagonist with a 6-fold increase in potency over previously reported antagonists.

Alternative Splicing↗