• The Korean Journal of Physiology and Pharmacology
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• 제7권3호
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• pp.169-174
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• 2003

${\gamma}$-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.

• The Korean Journal of Physiology
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• 제24권2호
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• pp.403-411
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• 1990

The present investigation was performed to see a possible influence of the dorsal raphe nucleus (DRN) on pancreatic exocrine secretion in anesthetized rats since the DRN had been known to exert a regulatory mechanism on sympathetic activity which was known to be very important for pancreatic exocrine secretion, particularly in rats. Twenty-nine Sprague-Dawley rats fasted for 24 hours were anesthetized by i.p. injection of 1 g/kg of urethane. The pancreatic duct was cannulated to collect pancreatic juice while bile juice was diverted into the jejunum. The duodenopyloric junction was tightly ligated. After surgery for collection of pancreatic exocrine secretion and recording of carotid blood pressure, a coaxial electrode was stereotaxically inserted in the DRN with a guide of a brain atlas. And then, electrical stimulus of biphasic square wave with 2 v, 2 msec, 40 Hz was applied on the electrode for 10 minutes. Pancreatic volume flow and protein output secreted in 10 min were measured. Either bilateral cervical vagotomy or spinal cord transection at the level of $C4{\sim}C5$ was performed 20 min prior to stimulation of the DRN. 1) Electrical stimulation of the DRN resulted in significant (p<0.05) increase in pancreatic volume flow and protein output. These stimulatory effects were not affected by cervical vagotomy but completely abolished by cervical cord transection. 2) Electrical stimulation of the DRN also resulted in significant (p<0.05) rise of blood pressure of the carotid artery. The hypertensive effect was not affected by cervical vagotomy but completely abolished by cervical cord transection. The results strongly suggest that the DRN, a part of the central serotonergic system, could exert a stimulatory influence on pancreatic exocrine secretion by increasing the sympathetic activity in anesthetized rats.

• Asian-Australasian Journal of Animal Sciences
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• 제2권3호
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• pp.177-178
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• 1989

• The Korean Journal of Physiology
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• 제30권2호
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• pp.219-229
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• 1996

In order to investigate intra-pancreatic cholinergic roles on insulin action in exocrine secretion, the pancreas was isolated from rats and continuously perfused with modified Krebs-Henseleit solution. Intra-arterial infusion of insulin (100 nM) or cholecystokinin (CCK, 14 pM) alone resulted in stimulation of the volume flow and amylase output. Also insulin potentiated the action of CCK in the exocrine secretion. Tetrodotoxin and atropine completely abolished the potentiating action of insulin and CCK as well as the action of insulin alone, but did not change the action of CCK alone. In order to see an effect of intra-pancreatic neural activation on the insulin action, electrical field stimulation (EFS) with parameters of 20 V, 2 msec and 8 Hz was applied to the isolated pancreas for 10 min under 2.5 or 18 mM glucose background. The EFS voltage-dependently elevated the flow rate and amylase output, and potentiated exocrine secretion in 18 mM glucose infusion compared with 2.5 mM glucose. The potentiating effects of EFS and 18 mM glucose were not observed in the streptozotocin-treated pancreas although it was perfused with 18 mM glucose. However, it was restored when the diabetic pancreas was perfused with porcine insulin(100 nM). Tetrodotoxin and atropine inhibited the pancreatic secretion induced by EFS with the background of 18 mM glucose. The results of present investigation indicate that the intra-pancreatic cholinergic tone exerts a stimulatory influence on the action of insulin in pancreatic exocrine secretion of rats.

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.217-221
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• 2003

To clarify the roles of gonadal steroids on pancreatic exocrine secretion, effects of progesterone and estradiol-$17{\beta}$ on spontaneous and secretagogue-induced exocrine response of isolated perfused rat pancreas were investigated. Intra-arterial infusion of progesterone resulted in significant increase of the spontaneous pancreatic fluid and amylase secretion dose-dependently. However, estradiol-$17{\beta}$ did not exert any influence on spontaneous pancreatic exocrine secretion. Exogenous secretin, cholecystokinin (CCK), and acetylcholine markedly stimulated pancreatic fluid and amylase secretion. Progesterone initially enhanced secretin-induced amylase secretion, but this stimulatory response declined thereafter to basal value. Moreover, secretin-induced fluid secretion was not affected by infusion of progesterone. Therefore, initial increase of secretion-induced amylase secretion by progesterone seems to be a non-specific action by washout effect of secretin. Estradiol-$17{\beta}$ failed to change the secretin-induced fluid and amylase secretion. Both progesterone and estradiol-$17{\beta}$ did not exert any influence on CCK-induced fluid and amylase secretion. Acetylcholine-induced exocrine secretion of isolated perfused pancreas also was not affected by intra-arterial infusion of progesterone or estradiol-$17{\beta}$. It is concluded from the above results that progesterone could enhance the spontaneous pancreatic fluid and amylase secretion of isolated perfused rat pancreas through non-genomic shortterm action, and that these effects could be masked by more potent stimulants such as secretin, CCK, and acetylcholine.

• 대한수의학회지
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• 제36권1호
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• pp.1-9
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• 1996

Functional and morphological characteristics of the exocrine pancreas in genetic model BB rat of insulin dependent diabetes medllitus(IDDM) were carried out. Wistar rat was used as control animal. Flow rate of pancreatic juice, output of amylase and protein, and plasma glucose and insulin levess were examined. Also light and ultrastructural characteristics of the exocrine pancreas were observed. Pancreatic flow rate, output of amylase and protein, and insulin level were lower;glucose level was higher comparing with those of the control Wistar rat. In Wistar rat, exocrine pancreas was typical light microscopically. Zymogen granules and cell organelles were well developed in fine structure. Cell size of the periinsular acini was larger, and number of zymogen granules were more than those of the teleinsular acini. Most acinar cells were dark cells which containe well-developed RER in their cytoplasm. On the other hand, some light cells which have the dilated RER cisterns were found. In BB rat exocrine pancreas, cell size of per-and tele-insular acini similar to that of Wistar rat. The number of light cells occupied 40-50% compairing with that of Wistar rat. Zymogen granules were lower in number than that of Wistar rat and divied into three types in morphological characteristics ; type I showing normal structure, type II showing the wide hallo and small electron dense core in center of the zymogen granule and type III not having the electron dense core in the zymogen granule. The present ratio of type I, type II and type III are less than 5%, 30-40% and more than 50%, respectively.

• Journal of Gastric Cancer
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• 제11권2호
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• pp.126-130
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• 2011

A composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is characterized by the co-existence of two adjacent, but histologically-distinct tumors in an organ. Composite glandular/exocrine-endocrine carcinomas are a special type of tumor comprised of common adenocarcinomas and neuroendocrine components that account for at least one-third of the entire tumor area. Composite tumors have been reported in a range of organs, but are relatively rare in the stomach. We report a case of a composite neuroendocrine carcinoma with an adenocarcinoma of the stomach (mixed exocrine-endocrine carcinoma), which was misdiagnosed as a giant submucosal tumor preoperatively based on esophagogastroduodenoscopy and a contrast-enhanced axial computed tomographic scan.

• Archives of Pharmacal Research
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• 제21권6호
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• pp.657-663
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• 1998

The enzyme responsible for the synthesis of nitric oxide (NO) from L-arginine in mammalian tissues is known as nitric oxide synthase (NOS) (EC.1.14.13.39). In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat pancreatic acinar cells. Treatment of rat pancreatic acinar cells with cholecystokinin-octapeptide (CCK-OP) resulted in an increase in the arginine conversion to citrulline, the amount of $NO_X$, the release of amylase, and the level of CGMP. Especially, CCK-OP-stimulated increase of arginine to citrulline transformation, the amount of $NO_X$, and CGMP level were completely counteracted by the inhibitor of NOS, NG-monomethyl-L-arginine (MMA), by contrast, that of amylase release was partially reduced. Furthermore, MMA-induced decrease of NOS activity and amylase release showed dose-dependent pattern. The data on the time course of CCK-OP-induced citrulline formation and CGMP rise indicate that NOS and guanylate cyclase were activated by treatment of CCK-OP. However, the mechanism of agonist-stimulated guanylate cyclase activation in acinar cells remains unknown. Therefore, activation of NOS is one of the early events in receptor-mediated cascade of reactions in pancreatic acinar cells and NO, not completely, but partially mediate pancreatic enzyme exocrine secretion.

• The Korean Journal of Physiology and Pharmacology
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• 제6권1호
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• pp.27-31
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• 2002

${\gamma}-Aminobutyric$ 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 $(10,\;30\;and\;100\;{\mu}mol/kg/h),$ 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 $(30\;{\mu}mol/kg/h)$ 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 $(10,\;30\;and\;100\;{\mu}mol/kg/h)$ also dose-dependently elevated pancreatic amylase secretion evoked by CCK alone. Bicuculline $(100\;{\mu}mol/kg/h),$ a $GABA_A-receptor$ 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 $GABA_A-receptor$ in anesthetized rats, which may account for elevating the action of CCK released by sodium oleate.

• 한국임상수의학회지
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• 제18권1호
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• pp.7-13
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• 2001

Depending on the degree of exocrine pancreatic insufficiency, there are inconsistent values in the serum trypsin-like immunoreactivity (TLI), hematology, and serology. To determine the correlation between those values and complete pancreatic insufficiency, 10 pancreatectomized dogs as the treated group and 10 sham operation dogs as control group were used. The entire treated group showed significant decrease in serum TLI level from 2.63$\pm$0.20 ng/ml (day 0) to 1.81$\pm$0.43 ng/ml at day 1 after the pancreatectomy (p<0.05) and the decline maintained till the end of the experiment. Blood glucose level gradually increased, but albumin level showed significant decrease (p<0.05) at day 1 and maintained the decline. Three clinical signs were observed such as depression, vomiting, and diarrhea. The entire treated group showed diarrhea throughout the experiment, but depression and vomiting were gradually diminished. The activity of serum alkaline phosphatase in the treated group increased till day 2 then decreased, on the other hand, control group showed continuous increase till day 4, and then decreased. Only experimental group showed the increased alanine aminotransferase activity at day 1. Serum lipase activity in the treated group jumped up at day 1 and then dropped down, which was even lower than the control. Regarding serum amlyase activity gradually decreased. According to these results, the assay of trypsin-like immunoreactivity showed the consistent result, so it suggests that TLI is an useful tool to determine the pancreatic exocrine function and possible diagnosis of exocrine pancreatic insufficiency compared to the simple assay of plasma amylase and lipase.