Taurine in the central nervous system and the mammalian actions of taurine

Nonsynaptic Glycine Receptor Activation during Early Neocortical Development

The gamma-aminobutyric acid (GABA) type A receptor system, the main fast-acting inhibitory neurotransmitter system in the brain, is the pharmacological target for many drugs used clinically to treat, for example, anxiety disorders and epilepsy, and to induce and maintain sedation, sleep, and anesthesia. These drugs facilitate the function of pentameric GABA(A) receptors that exhibit widespread expression in all brain regions and large structural and pharmacological heterogeneity as a result of composition from a repertoire of 19 subunit variants. One of the main problems in clinical use of GABA(A) receptor agonists is the development of tolerance. Most drugs, in long-term use and during withdrawal, have been associated with important modulations of the receptor subunit expression in brain-region-specific manner, participating in the mechanisms of tolerance and dependence. In most cases, the molecular mechanisms of regulation of subunit expression are poorly known, partly as a result of neurobiological adaptation to altered neuronal function. More knowledge has been obtained on the mechanisms of GABA(A) receptor trafficking and cell surface expression and the processes that may contribute to tolerance, although their possible pharmacological regulation is not known. Drug development for neuropsychiatric disorders, including epilepsy, alcoholism, schizophrenia, and anxiety, has been ongoing for several years. One key step to extend drug development related to GABA(A) receptors is likely to require deeper understanding of the adaptational mechanisms of neurons, receptors themselves with interacting proteins, and finally receptor subunits during drug action and in neuropsychiatric disease processes.

Regulation of GABA(A) receptor subunit expression by pharmacological agents.

Taurine and GABA release from mouse cerebral cortex slices: potassium stimulation releases more taurine than GABA from developing brain.

Ontogeny and distribution of GABAA receptors in rat brainstem and rostral brain regions

Development of taurine biosynthesizing system in cerebral cortical neurons in primary culture.

Development of γ-aminobutyric acid (GABA)ergic neurons in cerebral cortical neurons in primary culture

Effects of alcohol (ethanol) and acetaldehyde (AcAl) on the metabolism and function of gamma-amino-butyric acid (GABA)ergic and cholinergic systems were investigated using mouse cerebral cortical neurons in primary culture. Exposure to alcohol in vitro had no significant effects on the content of neuroactive amino acids as well as the activities of glutamic acid decarboxylase (GAD), GABA-transaminase (GABA-T), choline acetyltransferase (CAT) and acetylcholinesterase (AChE). In contrast, AcAl showed remarkable reductions of neuroactive amino acids content, and of CAT and AChE activities, but induced no alteration in the activities of GAD and GABA-T. [3H]Flunitrazepam [( 3H]FLN) binding and the stimulatory effect of GABA on [3H]FLN binding were found to be inhibited by in vitro exposure to both alcohol and AcAl, both of which, however, induced no changes in [3H]muscimol binding. These results suggest that the direct actions of AcAl on cholinergic systems in primary cultured neurons may be more potent than those of alcohol. The results described above also suggest that alcohol-induced neurochemical alterations in vivo may be, at least in part, caused by AcAl converted from alcohol in vivo.

Effects of alcohol and acetaldehyde on metabolism and function of neurotransmitter systems in cerebral cortical neurons in primary culture.

Development of cerebral cholinergic neurons in primary culture

Significance of the enhancement of GABA receptor binding with low affinity in the assessment of central effects of benzodiazepine derivatives: Analysis using a 1H-1,2,4-triazolyl benzophenone derivative (450191-S).

Shoichi Tomono

Papers

Development of taurine biosynthesizing system in cerebral cortical neurons in primary culture.

Development of γ-aminobutyric acid (GABA)ergic neurons in cerebral cortical neurons in primary culture

Effects of alcohol and acetaldehyde on metabolism and function of neurotransmitter systems in cerebral cortical neurons in primary culture.

Development of cerebral cholinergic neurons in primary culture

Significance of the enhancement of GABA receptor binding with low affinity in the assessment of central effects of benzodiazepine derivatives: Analysis using a 1H-1,2,4-triazolyl benzophenone derivative (450191-S).