Suppressive effect of gamma-aminobutyric acid (GABA) on histamine release in rat basophilic RBL-2H3 cells

Basophils and mast cells play a crucial role in immediate allergic reactions. These cells release various inflammatory mediators including histamine in response to binding of antigen to its specific IgE bound to the high affinity IgE receptor on the cell surface. In the present study, we examined the influence of gamma-aminobutyric acid (GABA) on histamine release in rat basophilic leukemia RBL-2H3 cells. After sensitization with anti-dinitrophenyl (DNP) IgE, challenge of RBL-2H3 cells with DNP-conjugated bovine serum albumin (DNP-BSA) caused a release of histamine in the cell suspension. The IgE-mediated histamine release was suppressed by GABA, with about 60% inhibition at 100 microM. In the same condition, baclofen, a GABAsub(B) receptor agonist, also inhibited histamine release. At a concentration of 100 microM, the inhibition rate of baclofen was approximate 80% of histamine release induced by DNP-BSA stimulation. In addition, these inhibitory effects of GABA and baclofen were attenuated by the addition of CGP35348, a GABAsub(B) receptor antagonist. These results suggest that GABA suppresses degranulation in basophils and mast cells via GABAsub(B) receptor.