Effects of gamma-aminobutyric acid on action of gastrin-releasing peptidergic neurons in exocrine secretion of isolated, perfused rat pancreas.

Abstract

gamma-Aminobutyric acid (GABA) has been reported to enhance exocrine secretion evoked by intrinsic neuronal excitation in the pancreas. To see the effect of GABA on the action of gastrin-releasing peptide (GRP)ergic neurons in exocrine secretion of the pancreas. 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. GABA (3, 10, 30 microM), given intra-arterially, elevated the EFS-evoked pancreatic secretions of fluid and amylase dose-dependently. An anti-GRP antiserum (10 microL/mL: titer of 1:66,000) reduced the GABA (10 microM)-enhanced EFS-evoked pancreatic secretions. Synthetic porcine GRP-27 (30, 100, 300 p ) increased the pancreatic secretions dose-dependently, and these were further elevated by GABA (10 microM). The anti-GRP antiserum also reduced the GABA-enhanced GRP (100 p )-induced pancreatic secretions. Bicuculline (10 microM) reduced the enhancing effect of GABA on pancreatic secretions evoked by EFS as well as GRP. 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.