Background & Aims: γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS) and it is produced via the enzymatic activity of glutamic acid decarboxylase (GAD). GABA generates fast biological signaling through type A receptors (GABAAR), an anionic channel. Intriguingly, GABA is found in the jejunum epithelium of rats. The present study intended to determine whether a functional GABA signaling system exists in the intestinal epithelium; and if so whether the GABA signaling regulates intestinal epithelial functions. Methods: RT-PCR, Western blot and immuno histochemical assays of small intestinal tissues of various species were performed to determine the expression of GABA-signaling proteins in intestinal epithelial cells. Perforated patch clamp recording was used to measure GABA-induced transmembrane current in the small intestine epithelial cell line IEC-18. The fluid weight to intestine length ratio was measured in mice that were treated with GABAAR agonist and antagonist. The effect of GABAAR antagonist on allergic diarrhea was examined using a mouse model.. Results: GABA, GAD and GABAAR subunits were identified in small intestine epithelial cells of mice, rats, pigs and human. GABAAR agonist induced an inward current and depolarized IEC-18. Both GABA and the GABAAR agonist musimol increased intestinal fluid secretion of rats. The increased intestinal secretion was largely decreased by the GABAAR antagonist picrotoxin or gabazine, but not by tetrodotoxin. The expression levels of GABA-signaling proteins were increased in the intestinal epithelium of mice that were sensitized and challenged with OVA. The OVA-treated mice exhibited diarrhea, which was alleviated by oral administration of gabazine or picrotoxin. . Conclusions: An endogenous autocinre GABAergic signaling exists in the mammalian intestinal epithelium, which up-regulates intestinal fluid secretion. The intestinal GABAergic signaling becomes intensified in allergic diarrhea, and inhibition of this GABA-signal system alleviates the allergic diarrhea.
- gama-aminobutyric acid
- intestinal epithelial cell
- electrolyte transport
- allergic diarrhea
- Copyright © 2012, American Journal of Physiology- Gastrointestinal and Liver Physiology