Ligands of the benzodiazepine binding site allosterically modulate g-aminobutyric acidA receptors. Their binding pocket is made up of amino acid residues located on both a and g subunits. We transiently expressed wild-type a1b2g2 and mutant GABAA receptors in human embryonic kidney 293 cells and determined their binding properties. Receptors containing the mutant aY209A showed ;40-fold decrease...

The central nervous system (CNS) is able to synthesize and/or metabolize steroid hormones. These neuroactive steroids are capable of modulating several brain functions and, among these, they seem to regulate the hypothalamic-pituitary-gonadal (HPG) axis. Indeed, recent observations have shown that 5 alpha-pregnane-3 alpha-ol-20-one (allopregnanolone), one of the most abundant naturally occurrin...

BACKGROUND Soft drugs are molecules that are purposefully designed to be rapidly metabolized (metabolically labile). In anesthesia, the soft drug is useful because it enables precise titration to effect and rapid recovery, which might allow swift and clear-headed recovery of consciousness and early home readiness. Propofol may cause delayed awakening after prolonged infusion. Propanidid and AZD...

BACKGROUND: Amino acids in the beta subunit contribute to the action of general anaesthetics on GABA(A) receptors. We have now characterized the phenotypic effect of two beta subunit mutations in the most abundant GABA(A) receptor subtype, alpha1beta2gamma2. RESULTS: The beta2(N265M) mutation in M2 decreased the modulatory actions of propofol, etomidate and enflurane, but not of alphaxalone, wh...

Thio, Liu Lin, Ananth Shanmugam, Keith Isenberg, and Kelvin Yamada. Benzodiazepines block 2-containing inhibitory glycine receptors in embryonic mouse hippocampal neurons. J Neurophysiol 90: 89–99, 2003. First published March 26, 2003; 10.1152/jn.00612.2002. Inhibitory glycine receptors (GlyRs) in the mammalian cortex probably contribute to brain development and to maintaining tonic inhibition....

BACKGROUND Adenosine analogs have been shown to produce antinociception after intrathecal administration. To determine the adenosine receptor subtype involved in spinal antinociception, the effects of selective agonists and an antagonist on the evoked potentials recorded from a neonatal rat spinal cord were studied. The measured potentials are a slow ventral root potential (slow VRP), which is ...

Ligands of the benzodiazepine binding site allosterically modulate gamma-aminobutyric acidA receptors. Their binding pocket is made up of amino acid residues located on both alpha and gamma subunits. We transiently expressed wild-type alpha1beta2gamma2 and mutant GABAA receptors in human embryonic kidney 293 cells and determined their binding properties. Receptors containing the mutant alphaY20...

Long-term potentiation (LTP) of excitatory transmission in the hippocampus has been extensively studied as a synaptic model of learning and memory. Here we report a new form of LTP in which inhibitory synaptic signals are potentiated following tetanic stimulation of an opioid-containing excitatory pathway in the presence of opioid antagonists. The lateral perforant path (LPP) was stimulated at ...