Effects of γ-Aminobutyric Acid (GABA) on Proliferation of the Gastric Cancer Cell Line, KATO III

γ-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the adult mammalian central nervous system, is also found in many peripheral non-neuronal tissues and is thought to have important physiologic functions in addition to neurotransmission. Recently, we reported that GABA is expressed at high levels in colonic tumor cells. Because GABA participates in proliferation of chondrocytes and of neurons in mammalian fetal brain, we studied the effects of GABA on proliferation of a gastric cancer cell line, KATO III. Reverse transcription-polymerase chain reaction analyses showed that KATO III cells express GAD65 mRNA, which is one of the two isoforms of the GABA synthesis enzyme glutamate decarboxylase (GAD). Immunohistochemical analyses revealed that GAD65 and GABA are produced in KATO III cells. Expression of mRNA for GABAA receptor subunits and the corresponding proteins was also observed. Analyses of bromodeoxyuridine incorporation into KATO III cells treated with GABAA receptor agonists and antagonists, including GABA, showed that GABA increases proliferation of KATO III cells via GABAA receptors. These data strongly suggest that KATO III cells can promote their own proliferation by activating GABAA receptors with GABA in an autocrine or a paracrine fashion.