Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat (original) (raw)

GABA metabolism controls inhibition efficacy in the mammalian CNS

Neuroscience Letters, 1996

The effects of changes in y-aminobutyric acid (GABA) metabolism on inhibitory processes was studied in the perforant path-dentate gyrus synapses in rat cortico-hippocampal slices, and in the monosynaptic-reflex circuit in isolated newborn rat spinal cord. GABA metabolism was modulated by pharmacological block of either the anabolic enzyme glutamate decarboxylase (GAD) or the catabolic enzyme GABA transaminase (GABA-T). The results support the notion that GABA concentration determines the efficacy of inhibition in these regions of the central nervous system (CNS).

GABA and bicuculline actions on mouse spinal cord and cortical neurons in cell culture

Brain Research, 1982

The neutral amino acid 7-aminobutyric acid (GABA) produced membrane hyperpolarization and increased membrane chloride ion conductance of spinal cord (SC) and cortical (CTX) neurons in cell culture. GABA dose response curves were obtained for SC neurons by pressure applying known concentrations of GABA from micropipettes with large tips (miniperfusion pipettes). GABA response threshold was about 2 #M and large responses were elicited at GABA concentrations greater than 10/tM. Bicuculline (B1CUC) (0.1-10/~M) reversibly antagonized GABA responses on both SC and CTX neurons with a half maximal inhibitory concentration of about 1 ttM. BICUC antagonism of GABA responses was competitive (Lineweaver-Burke analysis). These results are compared with data on GABA and BICUC displacement of [aH]GABA binding to membranes of SC and CTX neurons in cell culture. It is suggested that high affinity GABA receptors are likely to be relevant for postsynaptic GABA responses while low affinity GABA receptors may be presynaptic. 0006-8993/82/0000-0000/$02.75

Pharmacologically distinct GABAB receptors that mediate inhibition of GABA and glutamate release in human neocortex

British Journal of Pharmacology, 1997

The release of endogenous g-aminobutyric acid (GABA) and glutamic acid in the human brain has been investigated in synaptosomal preparations from fresh neocortical samples obtained from patients undergoing neurosurgery to reach deeply located tumours. 2 The basal out¯ows of GABA and glutamate from superfused synaptosomes were largely increased during depolarization with 15 mM KCl. The K +-evoked over¯ows of both amino acids were almost totally dependent on the presence of Ca 2+ in the superfusion medium. 3 The GABA B receptor agonist (7)-baclofen (1, 3 or 10 mM) inhibited the over¯ows of GABA and glutamate in a concentration-dependent manner. The inhibition caused by 10 mM of the agonist ranged from 45 ± 50%. 4 The eect of three selective GABA B receptor antagonists on the inhibition of the K +-evoked GABA and glutamate over¯ows elicited by 10 mM (7)-baclofen was investigated. Phaclofen antagonized (by about 50% at 100 mM; almost totally at 300 mM) the eect of (7)-baclofen on GABA over¯ow but did not modify the inhibition of glutamate release. The eect of (7)-baclofen on the K +-evoked GABA over¯ow was unaected by 3-amino-propyl (diethoxymethyl)phosphinic acid (CGP 35348; 10 or 100 mM); however, CGP 35348 (10 or 100 mM) antagonized (7)-baclofen (complete blockade at 100 mM) at the heteroreceptors on glutamatergic terminals. Finally, [3-[[(3,4-dichlorophenyl) methyl]amino]propyl] (diethoxymethyl) phosphinic aid (CGP 52432), 1 mM, blocked the GABA B autoreceptor, but was ineective at the heteroreceptors. The selectivity of CGP 52432 was lost at 30 mM, as the compound, at this concentration, inhibited completely the (7)-baclofen eect both on GABA and glutamate release. 5 It is concluded that GABA and glutamate release evoked by depolarization of human neocortex nerve terminals can be aected dierentially through pharmacologically distinct GABA B receptors.

Enhancement by anesthetic and convulsant barbiturates of GABA binding to rat brain synaptosomal membranes

The Journal of neuroscience : the official journal of the Society for Neuroscience, 1981

All of the anesthetic (amylobarbitone, butobarbitone, pentobarbitone, phenobarbitone, and secobarbitone) and convulsant (5-ethyl-5(3'-methylbut-2-enyl) barbituric acid (3M2B) and 5-ethyl-5-(2'-cyclohexylidene-ethyl) barbituric acid (CHEB) barbiturates tested enhanced the binding of GABA to a carefully prepared P2 membrane fraction from rat brain in a dose-dependent manner. These findings are in agreement with the potentiation of the inhibitory effects of GABA in many neuronal systems by both classes of barbiturates.

An intracellular study of the effects of GABA on frog tectal neurones in vitro

Neuroscience Letters, 1992

The effects of y-aminobutyric acid (GABA) on neurones of the amphibian optic tectum were studied with current-and voltage-clamp recording from an isolated preparation of the midbrain of the frog Rana temporaria. Bath-applied GABA (1 mM) enhanced depolarizing synaptic potentials evoked in layer 6 tectal neurones by orthodromic stimulation of the optic tract. GABA also facilitated Na*-and Ca2+-dependent action potentials elicited by intracellular injection of depolarizing current. These actions of GABA were associated with comparatively small changes in membrane potential and their reversal potential was dependent on the CI equilibrium potential. Changes in input resistance observed during application of GABA were small and in part accountable for by the rectifying properties of the cell membrane. Tetrodotoxin (TTX; 1/.tM) did not block the action of GABA on these neurones. These results show that externally applied GABA was able to raise directly the intrinsic excitability of frog tectal neurones and to enhance excitatory synaptic transmission elicited by stimulation of optic nerve fibres.