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