Search results for " GABA"
showing 10 items of 127 documents
[ 18 F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors
2001
5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [11C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [L8F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A t…
The GABAergic System and the Gastrointestinal Physiopathology.
2015
Since the first report about the presence of γ-aminobutyric acid (GABA) within the gastrointestinal (GI) tract, accumulating evidence strongly supports the widespread representation of the GABAergic system in the enteric milieu, underlining its potential multifunctional role in the regulation of GI functions in health and disease. GABA and GABA receptors are widely distributed throughout the GI tract, constituting a complex network likely regulating the diverse GI behaviour patterns, cooperating with other major neurotransmitters and mediators for maintaining GI homeostasis in physiologic and pathologic conditions. GABA is involved in the circuitry of the enteric nervous system, controlling…
Enhanced tonic GABAA inhibition in typical absence epilepsy
2009
The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired γ-aminobutyric acid (GABA)-ergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent 'tonic' inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT-1 in the genetic models tested, and GAT-1 is crucial in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best character…
The inhibitory neural circuitry as target of antiepileptic drugs.
2001
Impairments and defects in the inhibitory neurotransmission in the CNS can contribute to various seizure disorders, i.e., gamma-aminobutyric acid (GABA) and glycine as the main inhibitory neurotransmitters in the brain play a crucial role in some forms of epilepsy. Recent advances in deciphering the molecular basis of the GABAergic and glycinergic systems has been achieved by means of cloning techniques and gene targeting strategies in animals, contributing to the understanding of drug action. As well, several anticonvulsive substances emerged which target key molecules of the inhibitory systems. Employment of recombinant expression systems, including, but not restricted to the inhibitory c…
GABA transporters control GABAergic neurotransmission in the mouse subplate.
2015
The subplate is a transient layer between the cortical plate and intermediate zone in the developing cortex. Thalamo-cortical axons form temporary synapses on subplate neurons (SPns) before invading the cortical plate. Neuronal activity within the subplate is of critical importance for the development of neocortical circuits and architecture. Although both glutamatergic and GABAergic inputs on SPns were reported, short-term plasticity of GABAergic transmission has not been investigated yet. GABAergic postsynaptic currents (GPSCs) were recorded from SPns in coronal neocortical slices prepared from postnatal day 3-4 mice using whole-cell patch-clamp technique. Evoked GPSCs (eGPSCs) elicited b…
Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: Role of GABAA and GABAC receptors
2007
We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) …
Evaluation of Correlation between Sleep and Psychiatric Disorders in a Population of Night Shift Workers: A Pilot Study
2023
Background: Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common. It is important to remember that the sleep–wake cycle also plays a central role in the genesis of anxiety and depression. The aim of our study is to evaluate the association between sleep disturbances and anxiety and depression in a group of workers of both sexes who perform night shift work. Methods: Information on sleep disorders was collected by administering the Insomnia Severity Index (ISI) questionnaire. Statistical analysis was conducted using the Chi-square test to assess whether there were any differences between sex for those who…
Age-related differences of γ-aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle.
2021
Background: Enteric neurons undergo to functional changes during aging. We investigated the possible age-associated differences in enteric γ-aminobutyric acid (GABA)ergic transmission evaluating function and distribution of GABAergic receptors in human colon. Methods: Mechanical responses to GABA and GABA receptor agonists on slow phasic contractions were examined in vitro as changes in isometric tension in colonic muscle strips from young (<65 years old) and aged patients (>65 years old). GABAergic receptor expression was assessed by quantitative RT-PCR. Key Results: In both preparations GABA induced an excitatory effect, consisting in an increase in the basal tone, antagonized by th…
Drug interactions at GABA(A) receptors.
2002
Neurotransmitter receptor systems have been the focus of intensive pharmacological research for more than 20 years for basic and applied scientific reasons, but only recently has there been a better understanding of their key features. One of these systems includes the type A receptor for the gamma-aminobutyric acid (GABA), which forms an integral anion channel from a pentameric subunit assembly and mediates most of the fast inhibitory neurotransmission in the adult vertebrate central nervous system. Up to now, depending on the definition, 16-19 mammalian subunits have been cloned and localized on different genes. Their assembly into proteins in a poorly defined stoichiometry forms the basi…
RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy
2014
Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, and its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive and depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) are important factors for the coordination of cellular vesicle transport systems, and several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs are associated with autophagy. Employing C. elegans and human primary fibroblasts, we show that RAB3GAP1 and RAB3GAP2, which are components of the TBC domain-free RAB3GAP complex, influence protein aggregation and affect autophagy at basal an…