Suppressive Eff ect of γ-Aminobutyric Acid (GABA) on Histamine Release in Rat Basophilic RBL-2H3 Cells

γ-Aminobutyric acid (GABA), which is synthesized by glutamic acid decarboxylase from glutamic acid, is the main inhibitory neurotransmitter and plays a key role in modulating neuronal activity in mammalian central nervous system. Addit ional ly , GABA is considered to be a multifunctional molecule that has different situational functions in some nonneuronal tissues. GABA exerts its actions via three pharmacologically and structurally diff erent classes of GABA receptors: GABAA, GABAB and GABAC receptors (Bowery and Enna, 2000). GABAA and GABAC receptors are ligand gated Cl channels activated by the binding of GABA, whereas GABAB receptor belongs to members of the seven transmembrane G-protein-coupled receptor superfamily (Bowery et al., 2002). It is reported that oral administration of GABA to animal models for hypertension resulted in the decrease of their blood pressure without affecting their heart rates. In spontaneously hypertensive rats, low-dose (0.3 to 1.0 mg/kg, i.d.) GABA had a hypotensive eff ect, which may result from attenuation of sympathetic transmission through the activation of GABAB receptors at presynaptic or ganglionic sites (Kimura et al., 2002). The existence of GABAA and GABAB receptors has been demonstrated in the mammalian intestine and respiratory tract (Gentilini, et al., 1995, Luzzi. et al., 1985, 1987). Recently, it is reported that the GABAB receptor is functionally expressed in neutrophils, and acts as a chemoattractant receptor (Rane et al., 2005). Previous study revealed that GABA, through an activation of GABAB receptors, inhibits antigen-induced contractions of tracheal strips isolated from sensitized guineapigs. Tracheal contractile response is closely related with histamine release in basophils and mast cells. Both types of cells appear to play an important role by producing and releasing mediators such as histamine, leukotriene and cytokines during anaphylactic responses. These mediators are secreted from basophils and mast cells in response to act ivat ion through the spec i f ic receptors aga inst immunoglobulin (Ig)E, cytokines, complements or other functional molecules. It is therefore possible that GABAmediated inhibition of tracheal contractions is directly due to inhibition of histamine release in mast cells. However, there is few information available for effi cacies of GABA on basophils and mast cells. In the present study, we examined the inhibitory eff ect of GABA on histamine release in rat basophilic RBL-2H3 cells. If so, the possibility that GABA inhibits the release of histamine via GABAB receptor in RBL-2H3 cells was pharmacologically assessed by using baclofen, a GABAB receptor agonist , and CGP35348, a GABAB receptor antagonist.