Search results for "GABA Antagonists"
showing 10 items of 28 documents
Pharmacological heterogeneity of γ-aminobutyric acid receptors during development suggests distinct classes of rat cerebellar granule cells in situ
2001
The gamma-aminobutyric acid receptor (GABA(A)R) represents a ligand-gated Cl(-)-channel assembling as heteropentamere from 19 known subunits. Cerebellar granule cells contain a unique subset, namely the alpha1-, alpha6-, beta2-, gamma2- and delta-subunits. We studied their GABAergic pharmacology in situ using whole-cell patch-clamp recordings in brain slices and a modified Y-tube application system. The distribution of the EC50s for GABA in young (P8-P14) and medium aged animals (P15-P28) could be fitted with the sum of two Gaussian distributions with means of 60 and 185 microM and 27 and 214 microM, respectively. In older animals (P29-P48) the observed homogeneous range of sensitivities fi…
Altered morphological and electrophysiological properties of Cajal-Retzius cells in cerebral cortex of embryonic Presenilin-1 knockout mice
2004
Mutations of Presenilin-1 are the major cause of familial Alzheimer's disease. Presenilin-1 knockout (PS1-/-) mice develop severe cortical dysplasia related to human type 2 lissencephaly. This overmigration syndrome has been attributed to the premature loss of Cajal-Retzius cells (CRcs), pioneer neurons required for the termination of radial neuronal migration. To elucidate the potential cellular mechanisms responsible for this premature neuronal loss, we investigated the morphological and electrophysiological properties of visually identified CRcs of wild-type (WT) and PS1-/- mouse brains at embryonic day 16.5. The density of CRcs was substantially reduced in the cerebral cortex of PS1-/-.…
Prenatal diazepam exposure functionally alters the GABA(A) receptor that modulates [3H]noradrenaline release from rat hippocampal synaptosomes.
2002
In rats, exposure to diazepam (DZ) during the last week of gestation is associated with behavioral alterations (in some cases sexually dimorphic) that appear when the animals reach adulthood. This study was conducted to evaluate the effects of prenatal DZ exposure on the function of the gamma-aminobutyric (GABA)(A) receptor complex. The method used - perfusion of rat hippocampal nerve terminals labeled with [3H]noradrenaline (NA) - allowed us to evaluate the effects of DZ on a specific native GABA(A) receptor subtype which is located on hippocampal noradrenergic nerve endings and mediates the release of NA. Muscimol stimulated synaptosomal release of [3H]NA in a concentration-dependent mann…
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…
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) …
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…
The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.
1998
The amino acid gamma-aminobutyric-acid (GABA) prevails in the CNS as an inhibitory neurotransmitter that mediates most of its effects through fast GABA-gated Cl(-)-channels (GABAAR). Molecular biology uncovered the complex subunit architecture of this receptor channel, in which a pentameric assembly derived from five of at least 17 mammalian subunits, grouped in the six classes alpha, beta, gamma, delta, sigma and epsilon, permits a vast number of putative receptor isoforms. The subunit composition of a particular receptor determines the specific effects of allosterical modulators of the GABAARs like benzodiazepines (BZs), barbiturates, steroids, some convulsants, polyvalent cations, and et…
Intracellular Na+ concentration influences short-term plasticity of glutamate transporter-mediated currents in neocortical astrocytes.
2012
Fast synaptic transmission requires a rapid clearance of the released neurotransmitter from the extracellular space. Glial glutamate transporters (excitatory amino acid transporters, EAATs) strongly contribute to glutamate removal. In this work, we investigated the paired-pulse plasticity of synaptically activated, glutamate transporter-mediated currents (STCs) in cortical layer 2/3 astrocytes. STCs were elicited by local electrical stimulation in layer 4 in the presence of ionotropic glutamate (AMPA and NMDA), GABAA, and GABAB receptor antagonists. In experiments with low [Na+]i (5 mM) intrapipette solution, STCs elicited by paired-pulse stimulation demonstrated paired-pulse facilitation (…
Phencyclidine inhibits the activity of thalamic reticular gamma-aminobutyric acidergic neurons in rat brain.
2014
Póster presentado en el IX Simposi de Neurobiologia Experimental, celebrado los días 22 y 23 de octubre de 2014 en Barcelona y organizado por la Societat Catalana de Biologia del Institut d'Estudis Catalans
Comparative pharmacological activity of optical isomers of phenibut
2007
Phenibut (3-phenyl-4-aminobutyric acid) is a GABA (gamma-aminobutyric acid)-mimetic psychotropic drug which is clinically used in its racemic form. The aim of the present study was to compare the effects of racemic phenibut and its optical isomers in pharmacological tests and GABAB receptor binding studies. In pharmacological tests of locomotor activity, antidepressant and pain effects, S-phenibut was inactive in doses up to 500 mg/kg. In contrast, R-phenibut turned out to be two times more potent than racemic phenibut in most of the tests. In the forced swimming test, at a dose of 100 mg/kg only R-phenibut significantly decreased immobility time. Both R-phenibut and racemic phenibut showed…