Receptors and transmission in the brain-gut axis: potential for novel therapies. IV. GABA(B) receptors in the brain-gastroesophageal axis.

GABA(B) receptors are inhibitory G protein-coupled receptors that are commonly associated with presynaptic inhibition of transmitter release in the central nervous system. In the brain-gastroesophageal axis, a role has recently been demonstrated for GABA(B) receptors on extrinsic afferent endings within the stomach and esophagus, where they reduce mechanosensitivity. This action is compounded by inhibition of communication centrally from these afferents in the brain stem and within central circuits. There is a final peripheral action on the motor pathway where GABA(B) receptors reduce output of acetylcholine from vagal preganglionic motoneurons. These potent, multiple actions of GABA(B) receptors may have therapeutic benefit by reducing the triggering of transient lower esophageal relaxations, which are the major cause of gastroesophageal reflux. An important clinical application is therefore emerging for this recent discovery.