Effects of γ-Aminobutyric acid on action of gastrin-releasing peptidergic neurons in exocrine secretion of isolated, perfused rat pancreas

Introduction: γ-Aminobutyric acid (GABA) has been reported to enhance exocrine secretion evoked by intrinsic neuronal excitation in the pancreas. Aim: To see the effect of GABA on the action of gastrin-releasing peptide (GRP)ergic neurons in exocrine secretion of the pancreas. Methodology: Pancreatic neurons were excited by electrical field stimulation (EFS) in the isolated, perfused rat pancreas. GRP in the pancreatic circulation was neutralized by an anti-GRP antiserum to block GRPergic neuronal action on pancreatic exocrine secretion. Results: GABA (3, 10, 30 μM), given intra-arterially, elevated the EFS-evoked pancreatic secretions of fluid and amylase dose-dependently. An anti-GRP antiserum (10 μL/mL: titer of 1:66,000) reduced the GABA (10 μM)-enhanced EFS-evoked pancreatic secretions. Synthetic porcine GRP-27 (30, 100, 300 pM) increased the pancreatic secretions dose-dependently, and these were further elevated by GABA (10 μM). The anti-GRP antiserum also reduced the GABA-enhanced GRP (100 pM)-induced pancreatic secretions. Bicuculline (10 μM) reduced the enhancing effect of GABA on pancreatic secretions evoked by EFS as well as GRP. Conclusion: GABA enhances pancreatic secretions evoked by EFS as well as GRP, which is reduced by the anti-GRP antiserum. The enhancing effects of GABA on the EFS- and GRP-induced pancreatic secretions are diminished by bicuculline. The results indicate that GABA enhances intrinsic GRPergic neuronal action on exocrine secretion via the GABA A receptors in the rat pancreas.