Gastric habitation by Helicobacter pylori: insights into acid adaptation.

GABA A receptors are Cl Ϫ channels that can be opened by GABA and are the major inhibitory neurotransmitter receptors in the CNS. A variety of pharmacologically important drugs, such as benzodiazepines, barbiturates, neuroactive steroids, anesthetics and convulsants, produce at least part of their clinically relevant effects by interacting with distinct allosteric binding sites on GABA A receptors 1. GABA A receptors are composed of five subunits that can belong to different subunit classes. So far, at least six ␣-, three ␤-, three ␥-, one ␦-, one ⑀-, one ␲-, one ␪-and three ␳-subunits have been cloned from the mammalian nervous system 2,3 , and depending on their subunit composition, receptors exhibit distinct pharmacological and electro-physiological properties 1,2. Recent immunocytochemical studies have indicated that individual subunits exhibit a distinct and often widespread distribution throughout the nervous system 4,5. The resulting expression of multiple subunits in the same neurons suggest the existence of a large variety of GABA A receptor subtypes in the brain. Individual receptor subunits not only exhibit an expression pattern that is specific for certain neurons 4,5 , but also a distinct subcellular localiz-ation 4,6 , which suggests that different receptor subtypes might have specific functions. Owing to the promiscuity of the individual subunits, the actual identification of receptor subtypes has proved difficult. Recently, a subtractive purification method was established, which for the first time allowed determination of the subunit composition of native GABA A receptor subtypes 7,8. Combined with studies investigating the subunit stoichiometry 9 , results indicated that the majority of GABA A receptors comprise two ␣-, two ␤-, and one ␥-subunit 10. Minor receptors appear to be composed of ␣␤␦, ␣␤⑀, ␣␤␲, ␣␤ or homo-and hetero-oligomeric ␳-subunits 10. Because two different ␣-and/or two different ␤-subunits can be present in the same receptor, probably more than 500 distinct GABA A receptor subtypes exist in the brain. Owing to the widespread distribution and quantitative importance of the GABA system, even minor GABA A receptor subtypes probably exhibit an abundance that is comparable with that of some monoamine, 5-HT or peptide receptors. What is the function of individual GABA A receptor subtypes in the brain? One way to answer this question is to study the effects of a selective pharmacological modulation of a certain receptor subtype. Although a large variety of allosteric binding sites have been identified on GABA A receptors 1 , only a few compounds have …