• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.181-186
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• 2012

Fenofibrate is a selective peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) activator and is prescribed to treat hyperlipidemia. The mechanism through which $PPAR{\alpha}$ agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.

• Archives of Pharmacal Research
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• 제18권6호
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• pp.434-439
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• 1995

In pancreatic cells, NO formation is associated with increased levels of cGMP and endocrine/exocrine secretion. In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat pancreatic tissues. Treatment of rat pancreatic tissue with sholecystokinin-pancreozymin (CCK-PZ) resulted in an significant increase in arginine conversion to citruline, the amount of nitrite/nitrate, the release of amylase, and the level of cGMP. Furthermore, CCK-PZ stimulated increase of amylase release and conversion of arginine to citrulline transformation were counteracted by the inhibitor of NO synthase, $N^G-nitro-L-arginine$ methyl ester. The results on the time course of CCK-PZ-induced citrulline formation within the first seconds of simulation. The kinetics of citrulline accumulation correlate well with those of cGMP rise, which further confirms the conclusion that NO mediates the response to CCK-PZ by cGMP.

• 대한본초학회지
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• 제20권3호
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• pp.93-100
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• 2005

Objective : Patriniae Herba (PH) has long been used as a remedy for treating infectious diseases in Korea. In the present experiments, the author examined the effects of PH on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis (AP) in rats. Methods : Male Wistar rat weighing 200 to 250 g were divided into three groups. Normal untreated group, in treatment with PH group; PH (1g/kg) was administered orally, followed by $75\;{\mu}g/kg$ CCK subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 days. In treatment with saline group, the protocol was the same as in treatment group with PH. The author determined the pancreatic weight/body weight ratio, the levels of pancreatic HSP60, HSP72 and the secretion of pro-inflammatory cytokines. Methods : Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. PH was significantly decreased the pancreatic weight/body weight ratio in CCK-induced AP. Futhermore, the author demonstrated that PH increased HSP60 and HSP72 compared with CCK-induced AP. Additionally, the secretion of $TNF-{\alpha},\;IL-1{\beta}$ and IL-6 the levels of amylase and lipase were lower than that saline. Conclusions : These results suggest that PH may has a inhibitory effect against CCK-induced AP.

• 한국가금학회지
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• 제16권4호
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• pp.219-232
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• 1989

본 연구는 닭에 있어서 사료성분에 대한 췌장소화효소(amylase. trypsinogen 및 chymotrypsinogen) 분비기구에 대해서 검토했다. 먼저, 췌효소분비의 단기응답실험에 유용한 새로운 췌액채취법을 개발했다. 이 방법을 이용해서 아미노산 및 glucose를 날개정맥으로 투여한 결과 phenylalanine만이 trypsinogen 및 Chymotrypsinogen이 증가되었지만 그 외의 아미노산 및 glucose에 의해서는 분비증가 효과가 없었다. Cholecystokinin(CCK)투여 에 의해 췌효소분필는 즉각적으로 높은 분비반응을 보였으며, 이 반응은 또한 농도의존성을 나타냈다. CCK투여는 chymotrypsinogen의 쪽이 amylase 및 trypsinogen보다 높은 비율로 분비되는 선택적인 분비반응을 나타냈다. 아미노산과 CCK을 공동투여하면 첨가한 아미노산의 종류에 따라 췌효소분비반응은 여러 가지 형태로 증가되었지만 glucose와의 공동투여에서는 CCK 단독투여와 비교해서 차가 없었다. Valine과 arginine을 여러 가지 농도로 CCK와 공동 투여한 결과, valnine에서는 0.5mM일때, arginin에서는 5mM일때 가장 높은 분비반응을 보였다. 위의 결과로부터 아미노산의 조합에 의한 췌효소분비반응에 대해서 검토했다. 즉, 아미노산 mixture, threonine＋phenylalanine＋isoleucine, Threonine＋phenylalanine, threonine＋isoleucine 및 phenylalanine＋isoleucine과 CCK를 공동투여 했다. 각 물질을 투여한 후 50분간 분비한 효소를 비교하면, threonine＋phenylalanine에 의한 췌효소분비반응은 아미노산 mixture에 의한 분비반응과 동일하게 높은 반응을 보였다. 이상의 결과로부터 닭에 있어서 췌장소화효소분비는 CCK와 아미노산의 사이에 협동작용이 있으며, 그 협동작용은 아미노산의 종류에 따라 선택적인 분비반응을 함으로써 장내소화가 진행된다고 본다.

• 대한수의학회지
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• 제39권1호
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• pp.20-26
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• 1999

To investigate the regional distribution and relative frequency of the neurotensin-, pancreatic polypeptide(PP)- and gastrin/cholecystokinin(Gas/CCK)-immunoreactive cells in the gastrointestinal tract of the bullfrog(Rana catesbeiana) with developmental stages, group of bullfrogs subdivided into the tadpole with hindlegs, metamorphosed bullfrog with tail, 2 weeks after metamorphosed bullfrog and adult bullfrog, were stained by immunohistochemical methods (PAP methods). Neurotensin-immunoreactive cells were observed from the pylorus of the metamorphosed bullfrog with tail, but these cells were not detected after that periods. PP-immunoreactive cells were detected from the adult bullfrog in the pylorus, duodenum and ileum. These cells were most predominant in the pylorus. Gas/CCK-immunoreactive cells were observed from the adult bullfrog in the pylorus. According to these results, most of immunoreactive cells in the gastrointestinal tract of the bullfrog were appeared after the complete metamorphosed periods, in which the complete differentiation of structure of gastrointestinal tract were occurred, and variable changes of the regional distribution and relative frequency with developmental stages were observed.

• Asian-Australasian Journal of Animal Sciences
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• 제2권3호
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• pp.165-166
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• 1989

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 58th Annual Meeting of The Korean Society of Pharmacology
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• pp.63-63
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• 2006

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.83-90
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• 1997

Aim of this study was to investigate if pancreatic polypeptide (PP) reduced the insulin action via the intra-pancreatic cholinergic nerves in the isolated rat pancreas. The pancreas was isolated from rats and perfused with intra-arterial infusion of modified Krebs-Henseleit solution containing 2.5 mM glucose at a flow rate of 1.2 ml/min. Simultaneous intra-arterial infusion of insulin (100 nM) resulted inpotentiation of the pancreatic flow rate and amylase output which were stimulated by cholecystokinin (CCK, 14 pM). These potentiating actions of insulin on the CCK -stimulated pancreatic exocrine secretion were completely abolished by administration of rat PP. Vesamicol, a potent inhibitor of vesicular acetylcholine storage, and tetrodotoxin (TTX) also significantly reduced the combined actions of insulin and CCK. Administration of carbamylcholine, an acetylcholine agonist, completely restored the vesamicol- or TTX-induced inhibition of the potentiation between insulin and CCK. Also rat PP failed to attenuate the restoring effect of carbamylcholine. Electrical field stimulation (15-30 V, 2 msec and 8 Hz) resulted in a significant increase in the pancreatic flow rate and amylase output in voltage-dependent manner. Effects of electrical field stimulation were augmented by endogenous insulin. Rat PP also suppressed the pancreatic exocrine secretion stimulated by electrical field stimulation. These observations strongly suggest that PP inhibits the potentiating actions of insulin on CCK -stimulated pancreatic exocrine secretion by suppression of the intra-pancreatic cholinergic activity in the isolated rat pancreas.

• The Korean Journal of Physiology
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• 제25권1호
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• pp.27-35
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• 1991

Generally, it has been known that cholecystokinin (CCK) release into the plasma is under cholinergic control, but secretin release is not. Thus in anesthetized dogs we studied the effect of atropine $(50\;{\mu}g/kg\;followed\;by\;50\;{\mu}g/kg/hr)$ on pancreatic secretion and plasma concentrations of bioactive CCK and immunoreactive secretin in response to intraduodenal perfusion of sodium oleate (1, 3 and 9 mmol/hr). The volume, protein output and bicarbonate output of the secretion were increased by sodium cleats and this oleate-induced secretion was decreased significantly by atropine administration. However the increased plasma CCK and secretin levels by sodium oleate were not changed by atropine. These results indicate that atropine suppressed sodium oleate-induced pancreatic secretion through inhibiting cholinergic mechanism directly rather than decreasing the release of pancreatic secretory hormones. In another set of experiments, bilateral cervical vagi were stimulated electrically to observe the changes of pancreatic secretion and the above two plasma hormone levels in the presence or absence of atropine. In the vagally stimulated dogs, the volume, protein output and bicarbonate output of the pancreatic secretion were increased significantly. Both plasma secretin and CCK were concomitantly released significantly by vagal stimulation. Atropine significantly depressed the pancreatic secretory response as well as the release of these two pancreatic secretory hormones. Therefore, we conclude that in the presence of atropine the depressed pancreatic response to vagal stimulation is at least, in part, due to decreased release of endogenous CCK and secretin. In the vagally stimulated animals, however, the involvement of direct cholinergic influence on pancreatic exocrine gland remains to be answered.

• 대한약리학회지
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• 제30권1호
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• pp.39-48
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• 1994

포만중추 (satiety center)를 자극하여 음식섭취를 억제한다고 알려진 CCK-8을 흰쥐 복강에 투여하여, 흰쥐 뇌의 도파민 변화에 대한 CCK-8의 효과를 관찰하였다. 흰쥐 뇌의 부위별 도파민 함량은 HPLC-ECD방법으로 측정하였으며, 시상하부와 흑질에서의 TH-immunoreactive neuron은 면역조직화학법과 영상분석법을 시행하였다. 굶긴 쥐에서는 정상 쥐에 비하여, 도파민 함량이 전두 피질, 해마, 시상하부 및 편도체에서 각각 감소하였다. CCK-8을 투여한 쥐는 정상 쥐와 굶긴 쥐에 비하여, 도파민 함량이 시상하부에서 의미있게 감소하였다. 또한 굶긴 쥐는 정상 쥐와 비교하여, TH-positive neuron의 분포와 수가 뇌실옆핵, 깔때기핵, 정중융기 및 혹질에서 현저히 감소하였다. CCK-8투여시, 시상하부와 흑질에서의 TH-immunoreactive neuron의 수는 굶긴 쥐에 비하여 증가하였다. 이상의 실험 결과로 보아 음식물 섭취를 억제하는 작용이 있는 CCK-8은 시상하부의 도파민 신경계와 일부분 관련되어 있으며, 또한 시상하부와 흑질에 존재하는 TH-positive neuron은 음식물 섭취 행위에 중요한 역할이 있음을 시사하고 있다.