Reduced pregnane neurosteroids such as allopregnanolone and pregnanolone are potent neuromodulators able to affect a number of membrane receptors, including gamma-aminobutyric acid (GABA)(A), N-methyl-D-aspartate (NMDA), 5-hydroxytryptamine (5-HT)(3), and sigma(1) receptors. The present study used a drug discrimination procedure to assess further the receptor effects of pregnanolone in vivo. Ra...

inhibitory transmission in the mammalian central nervous system. GABA-A receptor belongs to the super-family of ligand-gated ion channels. It is assembled as a pentameric complex (i.e. composed of five subunits), arranged symmetrically to enclose the transmembrane chloride ion channel. Each subunit of GABA-A receptors consists of four trans-membrane domain (TM1-4) modulating the receptor activi...

The inhibitory neurotransmitter, GABA, activates a variety of receptors in all areas of the CNS. Two major subtypes of GABA receptors are well known: (1) GABAA receptors are ligand-gated Cl- channels that consist of a heteromeric mixture of protein subunits forming a pentameric structure, and (2) GABAB receptors couple to Ca2+ and K+ channels via G proteins and second messengers. Here, Graham J...

GABA release during cerebral energy deprivation (produced by anoxia or ischemia) has been suggested either to be neuroprotective, because GABA will hyperpolarize neurons and reduce release of excitotoxic glutamate, or to be neurotoxic, because activation of GABA(A) receptors facilitates Cl- entry into neurons and consequent cell swelling. We have used the GABA(A) receptors of hippocampal area C...

Whole cell patch-clamp recordings were obtained from thalamic ventrobasal (VB) and reticular (RTN) neurons in mouse brain slices. A bicuculline-sensitive tonic current was observed in VB, but not in RTN, neurons; this current was increased by the GABA(A) receptor agonist 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridine-3-ol (THIP; 0.1 microM) and decreased by Zn(2+) (50 microM) but was unaffected ...

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate brain. GABA activates both ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors in mammals. Whether non-mammalian vertebrates possess receptors with similar characteristics is not well understood. We used a mammalian GABA(B)-specific antagonist to determine the pharmacology of putative receptors in the...

Interactions between neurosteroids and GABA receptors have attracted particular attention in the supraoptic nucleus (SON). Although GABA(A) receptors (GABA(A)R) mediate a sustained tonic inhibitory current (I(tonic)), as well as conventional phasic inhibitory postsynaptic currents (IPSCs, I(phasic)) in the SON, whether the steroid modulation on I(tonic) is present in SON magnocelluar neurosecre...

We have developed a model of GABAergic synaptic transmission mediated by GABA A and GABA B receptors, including cooperativity in the G-protein cascade mediating the activation of K + channels by GABA B receptors. If the binding of several G-proteins is needed to activate the K + channels, then only a prolonged activation of GABA B receptors evoked detectable currents. This could occur if strong...

The GABA(A) receptors are the major inhibitory neurotransmitter receptors in mammalian brain. Each isoform consists of five homologous or identical subunits surrounding a central chloride ion-selective channel gated by GABA. How many isoforms of the receptor exist is far from clear. GABA(A) receptors located in the postsynaptic membrane mediate neuronal inhibition that occurs in the millisecond...

Futhan is a serine protease inhibitor and medicine in the treatment of disseminated intravascular coagulation (DIC) and acute pancreatitis. It is metabolized quickly in vivo. Here we show that Futhan reversibly inhibits NMDA receptors in hippocampal neurons and GABA(A) receptors both in hippocampal neurons and in A549 cells, a human alveolar epithelial cell line. The effect of Futhan on GABA(A)...