Effects of <FONT FACE= 바탕 >γ-Aminobutyric Acid on Intrinsic Cholinergic Action in Exocrine Secretion of Isolated, Perfused Rat Pancreas

Effects of <FONT FACE= 바탕 >γ-Aminobutyric Acid on Intrinsic Cholinergic Action in Exocrine Secretion of Isolated, Perfused Rat Pancreas

<FONT FACE= 바탕 >γ-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 (30<FONT FACE= 바탕 >μM) and muscimol (10<FONT FACE= 바탕 >μM), given intra-arterially, did not change spontaneous secretion but enhanced cholecystokinin (CCK; 10 pM)-induced secretions of fluid and amylase. GABA (3, 10, 30<FONT FACE= 바탕 >μM) further elevated EFS-evoked secretions of fluid and amylase dose-dependently. GABA (10, 30, 100<FONT FACE= 바탕 >μM) also further increased acetylcholine (5<FONT FACE= 바탕 >μM)-induced secretions of fluid and amylase in a dose-dependent manner. Bicuculline (10<FONT FACE= 바탕 >μM) effectively blocked the enhancing effects of GABA (30<FONT FACE= 바탕 >μM) on the pancreatic secretions evoked by either EFS or CCK. Both atropine (2<FONT FACE= 바탕 >μM) and tetrodotoxin (1<FONT FACE= 바탕 >μM) markedly reduced the GABA (10<FONT FACE= 바탕 >μM)-enhanced EFS- or CCK-induced pancreatic secretions. The results indicate that GABA enhances intrinsic cholinergic neuronal action on exocrine secretion via the GABA<SUB>A</SUB> receptors in the rat pancreas.