Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.