In the present study, the modulatory effect of AMPA receptors on gamma-aminobutyric acid (GABA) transporter current was investigated on enzymatically isolated horizontal cells of carp retina. The GABA transporter current elicited by 1 mmol/L GABA was decreased immediately after pre-application of AMPA (30 mumol/L or 3 mmol/L) for 50 s. Application of 10 mmol/L BAPTA in intracellular solution inhibited the suppression effect of AMPA on GABA transporter current. The suppression effect induced by co-application of 3 mmol/L AMPA and 3 mmol/L NMDA was similar to that of 3 mmol/L AMPA or 3 mmol/L NMDA alone. These results suggest that the activation of AMPA receptors inhibits GABA transporter-mediated current by affecting intracellular Ca(2+) processes in the retinal horizontal cells, which is identical with the modulatory effect of NMDA receptors on GABA transporters.
Animals ; Carps ; Egtazic Acid ; analogs & derivatives ; pharmacology ; GABA Plasma Membrane Transport Proteins ; metabolism ; Receptors, Ionotropic Glutamate ; metabolism ; Retinal Horizontal Cells ; metabolism ; gamma-Aminobutyric Acid ; pharmacology

OBJECTIVETo determine whether there are in vivo differences of metabolites levels in bilateral cortical masticatory area(CMA) of patients with sleep bruxism, compared with healthy controls using proton magnetic resonance spectroscopy(1H-MRS). Accordingly to explore if cortical control of the central jaw motor system is abnormal in sleep bruxism patients.

METHODSFifteen sleep bruxism patients and fifteen age- and gender-matched healthy controls underwent 1H-MRS of bilateral CMA using J-difference edited point-resolved spectroscopy sequence(MEGA-PRESS) technique. Levels of metabolites were quantified from the ratio of the metabolite integral to the unsuppressed water signal. Differences of levels of γ-aminobutyric acid(GABA), glutmate(Glu) and N-acetyl aspartate(NAA) in bilateral CMA between sleep bruxism patients and healthy controls were tested using two-way ANOVA.

RESULTSEdited spectra were successfully obtained from the bilateral CMA in all of the participants. Levels of GABA+, glutmate and NAA in right and left CMA in sleep bruxism patients were (2.45±0.48)×10(-3), (2.35±0.62)×10(-3), (10.65±1.84)×10(-3), (10.49±2.37)×10(-3), (10.70±3.61)×10(-3), and (11.26±4.01)×10(-3) respectively. In contrast, levels of GABA+, glutmate and NAA in right and left CMA in healthy controls were (2.63±0.68)×10(-3), (2.65±0.97)×10(-3), (11.19± 1.34)×10(-3), (10.58±3.14)×10(-3), (11.82±1.80)×10(-3), and (11.95±3.23)×10(-3). There were no differences in levels of GABA+(P=0.196), Glu(P=0.590), and NAA(P=0.292) between sleep bruxism patients and healthy controls, nor in inbilateral CMA(GABA+: P=0.837; Glu: P=0.510; NAA: P=0.628).

CONCLUSIONSThe results indicate the absence of any alteration of the cortical control of the central jaw motor system in the levels of GABA, Glu and NAA in patients with sleep bruxism.

Analysis of Variance ; Aspartic Acid ; analogs & derivatives ; analysis ; metabolism ; Case-Control Studies ; Glutamic Acid ; analysis ; metabolism ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; methods ; Masticatory Muscles ; metabolism ; physiopathology ; Motor Neurons ; metabolism ; Sleep Bruxism ; metabolism ; physiopathology ; gamma-Aminobutyric Acid ; analysis ; metabolism

OBJECTIVETo study the metabolic changes of auditory cortex in patients with presbycusis by using proton magnetic resonance spectroscopy ((1)H-MRS).

METHODSTen normal hearing volunteers (youth group), 10 normal hearing of elderly (aged group) and 8 patients with presbycusis (presbycusis group) were checked with proton magnetic resonance spectroscopy. N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho), γ-aminobutyric acid (GABA), glutamic acid (Glu) compound were measured. The differences between the groups were semi-quantitatively analyzed.

RESULTSWhen compared with youth group, reduced NAA/Cr, increased Cho/Cr were found in the aged group and presbycusis group (P < 0.05). GABA/Cr ratio and Glu/Cr ratio were significant difference between presbycusis group and youth group (P < 0.05). There were no significant difference in the GABA/Cr and Glu/Cr ratios in the bilateral auditory cortex between the youth group and the aged group (P > 0.05). When compared with aged group, the metabolic changes of auditory cortex in patients with presbycusis were remarkable (P < 0.05).

CONCLUSIONS(1)H-MRS is a noninvasive technique that can provide useful information concerning the metabolic changes of auditory cortex in human. In comparison to the aged group and the youth group, the changes of NAA, GABA, Cho and Glu is found in auditory cortex in patients with presbycusis.

Adult ; Aged ; Aspartic Acid ; analogs & derivatives ; metabolism ; Auditory Cortex ; metabolism ; Case-Control Studies ; Choline ; metabolism ; Creatine ; metabolism ; Female ; Glutamic Acid ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Presbycusis ; metabolism ; pathology ; Young Adult ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo study the effect of saikosaponins, the active ingredients of Bupleurum chinense DC. on glutamate and GABA expressions in the hippocampus of slow kindling rats induced by pentetrazole.

METHODSForty-eight healthy Sprague-Dawley rats were randomly divided into 6 equal groups, namely the blank control group (group A), normal saline (NS) group (group B), sodium valproate group (group C), and 3 saikosaponins groups of high, medium and small doses (groups D, E, and F, respectively). The rats in each group other than group A were given corresponding treatments after slow kindling by pentetrazole. After 4 weeks of treatment, the rats were sacrifices and the brain tissues were sampled, sliced and stained by immunohistochemically, and the results were analyzed according to the positive cell number and gray scale.

RESULTSIn CA1 region, the glutamate-positive cell number and gray scale of group B was significantly different from the other groups (P<0.05), but such difference was not observed in the CA2 and DG (P>0.05); In CA1, CA2 and DG of the hippocampus, the GABA-positive cell number of group B was significantly greater but the gray scale lower than those of the other groups (P<0.05). In CA1 and CA2 regions of the hippocampus, the glutamate- and GABA-positive cell ratio of group B was significantly lower than that of the other groups (P<0.05), but in CA1, CA2, and DG region of the hippocampus, the ratio of gray scale between glutamate- and GABA-positive cells was comparable between the groups (P>0.05).

CONCLUSIONThe expression of glutamate and GABA, especially the latter, increased in chronic kindling rat hippocampus. Saikosaponins intervene in such changes of glutamate and GABA to contain their expressions within normal range, which may be one of the mechanisms of saikosaponins to inhibit slow kindling induced by pentetrazole.

Animals ; Female ; Glutamic Acid ; biosynthesis ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Kindling, Neurologic ; metabolism ; Male ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; Pentylenetetrazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; gamma-Aminobutyric Acid ; biosynthesis

In this study, the "150-cavity", next to the H5N1 influenza virus neuraminidase activity site, has been used as the target to design and synthesize a structural analogue of chlorogenic acid, N-caffeoyl-GABA, using the flexible docking simulation. The docking study showed that the N-caffeoyl-GABA could be inserted into the "150-cavity" and combined with the Arg156 side chain by hydrogen bond. The best binding free energy of H5N1 NA-N-caffeoyl-GABA complex was -7.70 kcal mol(-1), equivalent that of the NA-oseltamivir. At the same time, using the H5N1 pseudotyping virus-based NA inhibitors screening model, we determined the inhibitory effect of oseltamivir, chlorogenic acid and N-caffeoyl-GABA on the NA. Compared with chlorogenic acid, N-caffeoyl-GABA significantly enhanced the inhibitory effect on NA, but less than oseltamivir. This study showed that the "150-cavity" could possibly be used as a new neuraminidase inhibitors target, and provided a path for the development of new neuraminidase inhibitors.
Antiviral Agents ; chemical synthesis ; pharmacology ; Caffeic Acids ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; pharmacology ; HEK293 Cells ; Humans ; Influenza A Virus, H5N1 Subtype ; enzymology ; Neuraminidase ; antagonists & inhibitors ; metabolism ; gamma-Aminobutyric Acid ; analogs & derivatives ; chemical synthesis ; pharmacology

Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.
Animals ; Ganglia, Spinal ; drug effects ; Male ; Nervous System Diseases ; chemically induced ; drug therapy ; Pregabalin ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; drug effects ; Taxoids ; adverse effects ; gamma-Aminobutyric Acid ; analogs & derivatives ; pharmacology

A growing number of studies have shown that arginine vasopressin (AVP) plays an analgesia role in the modulation of nociception. Previous studies have focused on the central mechanisms of AVP analgesia. The aim of the present study was to find out whether peripheral mechanisms are also involved. The effect of AVP on GABA-activated currents (IGABA) and GABAA receptor function in freshly isolated dorsal root ganglion (DRG) neurons of rats were studied using whole cell patch clamp technique. The result showed that, IGABA were potentiated by pre-treatment with AVP (1 × 10⁻¹⁰-1 × 10⁻⁵ mol/L) in a concentration-dependent manner. Meanwhile, the GABA concentration-response curve was shifted upwards, with an increase of (49.1 ± 4.0)% in the maximal current response but with no significant change in the EC50 values. These results indicate that the enhancing effect is non-competitive. In addition, the effects of AVP on IGABA might be voltage-independent. This potentiation of IGABA induced by AVP was almost completely blocked by the V1a receptor antagonist SR49059 (3 × 10⁻⁶ mol/L). Also it could be removed by intracellular dialysis of either GDP-β-S (5 × 10⁻⁴mol/L), a non-hydrolyzable GDP analog, or GF109203X (2 × 10⁻⁶ mol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp. These results suggest that AVP up-regulates the function of the GABAA receptor via G protein-coupled receptors and PKC-dependent signal pathways in rat DRG neurons, and this potentiation may underlie the analgesia induced by AVP.
Animals ; Arginine Vasopressin ; pharmacology ; Ganglia, Spinal ; cytology ; Guanosine Diphosphate ; analogs & derivatives ; pharmacology ; Indoles ; Maleimides ; Membrane Potentials ; Neurons ; drug effects ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; metabolism ; Signal Transduction ; Thionucleotides ; pharmacology ; gamma-Aminobutyric Acid ; pharmacology

No abstract available.
Acetic Acids/adverse effects/pharmacology ; Anticonvulsants/adverse effects/*pharmacology ; Carbamazepine/adverse effects/analogs & derivatives/pharmacology ; Clinical Trials ; Forecasting ; Fructose/adverse effects/analogs & derivatives/pharmacology ; Human ; Isoxazoles/adverse effects/pharmacology ; Propylene Glycols/adverse effects/pharmacology ; Triazines/adverse effects/pharmacology ; Vigabatrin ; gamma-Aminobutyric Acid/adverse effects/analogs & derivatives/pharmacology

PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Aged ; Aged, 80 and over ; Drug Therapy, Combination/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee/*drug therapy ; Pain Measurement ; Thiazines/administration & dosage/adverse effects/*therapeutic use ; Thiazoles/administration & dosage/adverse effects/*therapeutic use ; gamma-Aminobutyric Acid/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.
gamma-Aminobutyric Acid/metabolism ; Taurine/analogs & derivatives/therapeutic use ; Recurrence ; Receptors, Opioid, mu/genetics/metabolism ; Receptors, Opioid/antagonists & inhibitors ; Polymorphism, Genetic ; Neurons/metabolism ; Naltrexone/therapeutic use ; N-Methylaspartate/metabolism ; Models, Neurological ; Models, Biological ; Humans ; Glutamine/metabolism ; Disulfiram/therapeutic use ; Alcoholism/*drug therapy ; Alcohol Deterrents/*therapeutic use