The GABAergic System and the Gastrointestinal Physiopathology

Since the first report about the presence of γ-aminobutyric acid (GABA) within the gastrointestinal (GI) tract, accumulating evidence strongly supports the widespread representation of the GABAergic system in the enteric milieu, underlining its potential multifunctional role in the regulation of GI functions in health and disease. GABA and GABA receptors are widely distributed throughout the GI tract, constituting a complex network likely regulating the diverse GI behaviour patterns, cooperating with other major neurotransmitters and mediators for maintaining GI homeostasis in physiologic and pathologic conditions. GABA is involved in the circuitry of the enteric nervous system, controlling GI secretion and motility, as well as in the GI endocrine system, possibly acting as a autocrine/paracrine or hormonal agent. Furthermore, a series of investigations addresses the GABAergic system as a potential powerful modulator of GI visceral pain processing, enteric immune system and carcinogenesis. Although overall such actions may imply the consideration of the GABAergic system as a novel therapeutic target in different GI pathologic states, including GI motor and secretory diseases and different enteric inflammatory- and pain-related pathologies, current clinical applications of GABAergic drugs are scarce. Thus, in an attempt to propel novel scientific efforts addressing the detailed characterization of the GABAergic signaling in the GI tract, and consequently the development of novel strategies for the treatment of different GI disorders, we reviewed and discussed the current evidence about GABA actions in the enteric environment, with a particular focus on their possible therapeutic implications.