YAmino Butyric Acid

y-Amino butyric acid (GABA) has a major inhibitory role in the CNS, which mediates its effect via three classes of receptors, the ionotropic GABAA, GABAC receptors, and the G-protein-coupled GABAB receptors. GABAB receptor agonists inhibit vagal afferent mechanosensitivity in the upper gastrointestinal tract and GABAB receptors are expressed on gastric vagal afferent neurons. This peripheral action is associated with a reduction in triggering of transient lower esophageal relaxations (TLESRs) (87,176-179), which are the major cause of acid reflux. This has led to interest in these receptors as therapeutic targets for gastroesophageal reflux disease by reducing TLESRs and therefore reflux episodes. More recently, inhibitory actions of GABAB receptors have been demonstrated on pelvic afferents from rat colon (180), suggesting they may have a peripheral antinociceptive action. Endogenous activation of peripheral GABAB receptors on afferent endings is probably minimal, whereas endogenous GABA release is much more important in the CNS. Thus peripheral GABAb receptors may provide a naive but convenient target for reducing afferent excitability.

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