Julia H. White Fiona H. Marshall 7TMReceptor Systems, Molecular Pharmacology Dept, GlaxoWellcome Research and Development, Medicines Research Centre, Stevenage, Hertfordshire, UK SG1 2NY. Recent advances in GABA receptor biology have resulted in elucidation of the molecular structure of a GABAB protein with similarity to metabotropic glutamate receptors (mGluRs), GABAB(1) (Ref. 1), and the subs...

The nocioceptive information carried by neurons of the pontine parabrachial nucleus to neurons of the lateral division of the central amydala (CeA-L) is thought to contribute to the affective components of pain and is required for the formation of conditioned-fear memories. Importantly, excitatory transmission between parabrachial axon terminals and CeA-L neurons can be inhibited by a number of...

Brain nicotinic acetylcholine receptors (nAChRs) reportedly suppress the micturition, but mechanisms responsible for this suppression remain unclear. We previously reported that intracerebroventricularly administered (±)-epibatidine (non-selective nAChR agonist) activated sympatho-adrenomedullary system, which can affect micturition. Therefore, we investigated (1) whether (±)-epibatidine-induce...

Activation of K(+) channels by the G protein βγ subunits is an important signaling mechanism of G-protein-coupled receptors. Typically, receptor-activated K(+) currents desensitize in the sustained presence of agonists to avoid excessive effects on cellular activity. The auxiliary GABAB receptor subunit KCTD12 induces fast and pronounced desensitization of the K(+) current response. Using prote...

GABAB receptor activation modulates neuronal activity mediated by multiple CNS transmitters and can occur at pre- and postsynaptic sites. In low concentrations, baclofen acts presynaptically to diminish transmitter release via both hetero- and autoreceptors, whereas at increasing concentrations, the same compound alters postsynaptic membrane excitability by inducing a membrane hyperpolarization...

BACKGROUND The activation of GABAB receptors in the ventral tegmental area (VTA) has been suggested to attenuate the rewarding properties of psychostimulants, including nicotine. However, the neurochemical mechanism that underlie this effect remains unknown. Since GABAB receptors modulate the release of several neurotransmitters in the mammalian brain, we have characterised the effect of the GA...

Release of excitatory transmitter from boutons on crayfish nerve terminals was inhibited by (R,S)-baclofen, an agonist at GABAB receptors. Baclofen had no postsynaptic actions as it reduced quantal content without affecting quantal amplitude. The effect of baclofen increased with concentration producing 18% inhibition at 10 microM; EC50, 50% inhibition at 30 microM; maximal inhibition, 85% at 1...

Activation of GABAB receptors in the Xenopus embryo, a simple vertebrate, causes presynaptic inhibition of transmitter release from glycinergic spinal neurons and an increase in action potential threshold. To investigate the underlying mechanisms of GABAB receptor action, we have made whole-cell voltage-clamp recordings from acutely isolated Xenopus embryo spinal neurons. The GABAB receptor ago...

Temporal lobe epilepsy is the most common partial epilepsy syndrome seen in adult humans. The hippocampus is a key structure in the evolution of temporal lobe seizures. The axons of the dentate granule cells, the mossy fibres, constitute a major hippocampal excitatory input. Inhibitory phenomena at mossy fibre synapses may therefore prevent seizure propagation through the hippocampus. One such ...