Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)₃ receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC₅₀ value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT₃-mediated currents evoked by 1 mM dopamine, a partial 5-HT₃ receptor agonist, were inhibited by lamotrigine co-application. The EC₅₀ of 5-HT for 5-HT₃ receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT₃ receptor desensitization, inhibited 5-HT₃ receptor currents in a concentration-dependent manner. The deactivation of 5-HT₃ receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT₃ receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT₃-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.
Dopamine ; Epilepsy ; Neuroblastoma* ; Receptors, Serotonin, 5-HT3 ; Serotonin

The effect of forskolin on corticostriatal synaptic transmission was examined by recording excitatory postsynaptic currents (EPSCs) in rat brain slices using the whole-cell voltage-clamp technique. Forskolin produced a dose-dependent increase of corticostriatal EPSCs (1, 3, 10, and 30micrometer) immediately after its treatment, and the increase at 10 and 30micrometer was maintained even after its washout. When the brain slices were pre-treated with (DL)-2-amino-5-phosphonovaleric acid (AP-V, 100micrometer), an NMDA receptor antagonist, the acute effect of forskolin (10micrometer) was blocked. However, after washout of forskolin, an increase of corticostriatal EPSCs was still observed even in the presence of AP-V. When KT 5720 (5micrometer), a protein kinase A (PKA) inhibitor, was applied through the patch pipette, forskolin (10micrometer) increased corticostriatal EPSCs, but this increase was not maintained. When forskolin was applied together with AP-V and KT 5720, both the increase and maintenance of the corticostriatal EPSCs were blocked. These results suggest that forskolin activates both NMDA receptors and PKA, however, in a different manner.
Animals ; Brain ; Carbazoles ; Cyclic AMP-Dependent Protein Kinases ; Excitatory Postsynaptic Potentials ; Forskolin ; N-Methylaspartate ; Patch-Clamp Techniques ; Pyrroles ; Rats ; Receptors, N-Methyl-D-Aspartate ; Synaptic Transmission

The striatum receives glutamatergic afferents from the cortex and thalamus, and these synaptic transmissions are mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to characterize glutamate receptors by analyzing NMDA/AMPA ratio and rectification of AMPA and NMDA excitatory postsynaptic currents (EPSCs) using a whole-cell voltage-clamp method in the dorsal striatum. Receptor antagonists were used to isolate receptor or subunit specific EPSC, such as (DL)-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, ifenprodil, an NR2B antagonist, CNQX, an AMPA receptor antagonist and IEM-1460, a GluR2-lacking AMPA receptor blocker. AMPA and NMDA EPSCs were recorded at -70 and +40 mV, respectively. Rectification index was calculated by current ratio of EPSCs between +50 and -50 mV. NMDA/AMPA ratio was 0.20+/-0.05, AMPA receptor ratio of GluR2-lacking/GluR2-containing subunit was 0.26+/-0.05 and NMDA receptor ratio of NR2B/NR2A subunit was 0.32+/-0.03. The rectification index (control 2.39+/-0.27) was decreased in the presence of both APV and combination of APV and IEM-1460 (1.02+/-0.11 and 0.93+/-0.09, respectively). These results suggest that the major components of the striatal glutamate receptors are GluR2-containing AMPA receptors and NR2A-containing NMDA receptors. Our results may provide useful information for corticostriatal synaptic transmission and plasticity studies.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Adamantane ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Animals ; Excitatory Postsynaptic Potentials ; N-Methylaspartate ; Piperidines ; Plastics ; Rats ; Receptors, AMPA ; Receptors, Glutamate ; Receptors, N-Methyl-D-Aspartate ; Synaptic Transmission ; Thalamus

A 35-year old male developed epigastric pain and hematemesis one week before admission. Esophagogastroduodenoscopy was performed and a communication between the esophagus and another opening was discovered. On a follow-up CT and barium esophagogram, a tubular duplication was suspected and the patient was referred to the department of cardio-thoracic surgery. A pathological diagnosis of esophageal duplication (tubular type) was established. The patient was discharged and is currently being followed up. Esophageal duplication is a rare congenital malformation. Moreover, it has not heen reported in Korea that esophageal duplication presents with hematemesis.
Adult ; Barium ; Diagnosis ; Endoscopy, Digestive System ; Esophagus ; Follow-Up Studies ; Hematemesis* ; Humans ; Korea ; Male

OBJECTIVES: The authors recently found a suggestive evidence of linkage of chromosome 8p21-12 to schizophrenia in Korean multiplex families. Neuregulin 1 (NRG1) was identified in this locus as a positional and functional candidate gene for schizophrenia, through several independent studies with European and Chinese populations. The purpose of this study is to determine whether NRG1 is associated with schizophrenia in Korean population. METHODS: Three SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177) and two microsatellites markers (478B14-848, 420M9-1395) located at the 5' end of NRG1 were genotyped for 242 unrelated schizophrenia patients and the same number of normal controls. Genetic association was tested by chi2-test (df=1). Not only for the whole patients group but also for a subgroup of patients with auditory hallucination. This subtype showed stronger linkage with chromosome 8p12 in the prior study of the authors with multiplex families. RESULTS: G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with auditory hallucination compared to the control group (p=0.03, OR=1.76). We also found that 3 SNPs haplotype TTC (p=0.04, OR=0.58) and five markers haplotype TTC53 (p=0.01, OR=0.49) were associated with schziophrenia with a protective effect. Three SNPs haplotype CGT which is a part of the at-risk haplotype of the Icelandic schizophrenia families was found in excess in the patients group but no significant association was observed. CONCLUSION: NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium with a causal locus of this illness.
Alleles ; Asian Continental Ancestry Group ; Genetic Variation* ; Hallucinations ; Haplotypes ; Humans ; Iceland ; Linkage Disequilibrium ; Microsatellite Repeats ; Neuregulin-1* ; Polymorphism, Single Nucleotide ; Schizophrenia*

PURPOSE: The role of angiodysplasia as a main cause of upper gastrointestinal hemorrhage (UGH) in patients with chronic renal failure (CRF) is controversial. We investigated the sources of UGH and the clinical characteristics of UGH in patients with CRF. METHODS: We reviewed the medical and endoscopic records of 574 patients who were admitted to Gil Medical Center from November 1999 to November 2004. UGH was defined as hematemesis, or nasogastric aspirate showing fresh or old blood, or melena associated with acute drop in hematocrit. CRF was defined as a serum creatinine clearance < or =59 mL/min for at least 3 months before and after the bleeding episode or the patients who have undergone dialysis or received renal transplantation. RESULTS: Thirty-two of 574 patients were CRF group. 19 of the CRF patients have received dialysis (18 paitents-hemodialysis; 1 patient-peritoneal dialysis). The mean age of CRF group was 56+/-13.65 years old and 16 patients were male. The causes of UGH in CRF patients, in order of frequency, was duodenal ulcer (37.5%), gastric ulcer (34.4%), unknown (12.5%). No angiodyplasia was found in CRF group. The sources of bleeding did not differ significantly between the two groups. The prevalence of taking ulcerogenic drugs in CRF patients was higher than that in control group (59.4% vs 29.7%, p=0.001). The prevalence of Helicobacter pylori (H. pylori) infection in CRF patients with peptic ulcer and gastritis was lower than that in control group (16.7% vs 42.3%, p=0.017). The mean length of hospital stay and the mean numbers of blood transfusions required were higher in the CRF group than control group. However, no differences were seen between the two groups in mortality, recurrent bleeding and surgery for control of bleeding. CONCLUSION: The common cause of UGH in patients with CRF was peptic ulcer disease and no angiodysplasia was found.
Angiodysplasia* ; Blood Transfusion ; Creatinine ; Dialysis ; Duodenal Ulcer ; Gastritis ; Gastrointestinal Hemorrhage* ; Helicobacter pylori ; Hematemesis ; Hematocrit ; Hemorrhage ; Humans ; Kidney Failure, Chronic* ; Kidney Transplantation ; Length of Stay ; Male ; Melena ; Mortality ; Peptic Ulcer ; Prevalence ; Stomach Ulcer