Effects of gamma-Aminobutyric Acid on Intrinsic Cholinergic Action in Exocrine Secretion of Isolated, Perfused Rat Pancreas

gamma-Aminobutyric acid (GABA) has been reported to enhance exocrine secretion evoked not only by secretagogues but also by intrinsic neuronal excitation in the pancreas. The pancreas contains cholinergic neurons abundantly that exert a stimulatory role in exocrine secretion. This study was undertaken to examine effects of GABA on an action of cholinergic neurons in exocrine secretion of the pancreas. Intrinsic neurons were excited by electrical field stimulation (EFS; 15 V, 2 msec, 8 Hz, 45 min) in the isolated, perfused rat pancreas. Tetrodotoxin or atropine was used to block neuronal or cholinergic action. Acetylcholine was infused to mimic cholinergic excitation. GABA (30microM) and muscimol (10microM), given intra-arterially, did not change spontaneous secretion but enhanced cholecystokinin (CCK; 10 pM) -induced secretions of fluid and amylase. GABA (3, 10, 30microM) further elevated EFS-evoked secretions of fluid and amylase dose-dependently. GABA (10, 30, 100microM) also further increased acetylcholine (5microM) -induced secretions of fluid and amylase in a dose-dependent manner. Bicuculline (10microM) effectively blocked the enhancing effects of GABA (30microM) on the pancreatic secretions evoked by either EFS or CCK. Both atropine (2microM) and tetrodotoxin (1microM) markedly reduced the GABA (10microM) -enhanced EFS- or CCK-induced pancreatic secretions. The results indicate that GABA enhances intrinsic cholinergic neuronal action on exocrine secretion via the GABAA receptors in the rat pancreas.

Effects of gamma-Aminobutyric Acid on Pancreatic Amylase Secretion Evoked by Sodium Oleate in Anesthetized Rats

gamma-Aminobutyric Acid (GABA) is contained in pancreatic islet beta-cells although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA (10, 30 and 100micromol/kg/h), given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA (30micromol/kg/h) also further increased the amylase secretion stimulated by CCK+(30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA (10, 30 and 100micromol/kg/h) also dose-dependently elevated pancreatic amylase secretion evoked by CCK+alone. Bicuculline (100micromol/kg/h), a GABAA-receptor antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK+plus secretin or CCK+alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via GABAA-receptors in anesthetized rats, which may account for elevating the action of CCK+released by sodium oleate.