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.

Distribution, content and molecular heterogeneity of gastrin-releasing peptide in rat pancreas

Although importance of intrapancreatic neurons containing gastrin-releasing peptide (GRP) in control of exocrine secretion has been raised, the nature of GRP in the pancreas is unclear Thus, the present study was undertaken to see distribution, content and molecular heterogeneity of immunoreactive GRP in the rat pancreas Content of immunoreactive GRP in the rat pancreas was 2 99 +/- 0.66 ng/g wet tissues determined by radioimmunoassay. Immunoreactive GRP was most abundantly expressed in the duodenal part among 3 parts of the pancreas, duodenal, body and splenic part. Vagotomy failed to change the content of immunoreactive GRP in the pancreas. Three distinct forms of immunoreactive GRP, very identical to GRP-27, bombesin-24 and neuromedin C, were observed in the rat pancreas by using reversed phase C18 HPLC and Sephadex G-50 superfine column chromatography. Cell bodies of neurons containing immunoreactive GRP were scattered in pancreatic connective tissues and their nerve fibers innerv ated pancreatic acini and large ducts as determined by immunohistochemistry. The present results suggest that three distinct forms of GRP exist in intrapancreatic GRPergic neurons, which exert a stimulatory role in pancreatic exocrine secretion in rats.

Further characterization of bombesin like immunoreactivities from the skin of Korean fire-bellied toad, Bombina orientalis

Previously, we have isolated authentic bombesin and another bombesin like peptide named bombesin like immunoreactivity (BLI)-K2 from the skin of Korean fire-bellied toad, Bombina orientalis. In the present study, we have newly purified three heterogeneous forms of BLI named BLI-K3, BLI-K4, and BLI-K5 from side fractions obtained in previous isolation of bombesin like peptide. The BLIs were separated into five peaks on a column of C18 preparative HPLC. Among them, three minor peaks containing BLI-K3, K4, and K5 were purified by means of sequential chromatography on the columns of SP cation exchange HPLC and C18 reverse phase HPLC. The purified BLI-K3 and K4 showed high binding affinity to an anti-bombesin serum (LBE 2G-2) with binding potency of 72 and 95%, respectively, relative to that of bombesin. However, they did not possess any distinctive biological activity of bombesin like peptide. On the contrary, the biological activity of BLI-K5 was similar to that of bombesin but its binding affinity to an anti-bombesin serum was low. The results indicate that three heterogeneous forms of BLI were coexpressed with bombesin and BLI-K2 in the skin of B. orientalis. All forms of the purified BLI in the present study were immunologically active but only BLI-K5 possessed the distinctive biological activity of bombesin like peptide.

Effects of total parenteral nutrition and enteral nutrition on pancreatic exocrine secretion and severe acute pancreatitis / 肠外与肠内营养

This review examines the effects of parenteral nutrition(PN) or enteral nutrition(EN) on pancreatic exocrine secretion and severe acute pancreatitis(SAP). There is no evidence that PN support in SAP affects the underlying disease process,but it may prevent the malnutrition and complications.In recent years,EN is considered to be used in that it preserves gut barrier function.PN,in contrast,may result in mucosal atrophy,bacterial translocation and increased rates of catheter related sepsis.The effects of EN on pancreatic exocrine secretion and natural course of SAP are discussed.The safety and feasibility of EN in SAP have been established. EN may even be superior to PN.Some patients,however,cannot tolerate enteral feeding and PN still has a role.