Role of Endogenous Cholecystokinin and Cholecystokinin-A Receptors in the Development of Acute Pancreatitis in Rats

Tachibana, Issei; Shirohara, Hisashi; Czakó, László; Akiyama, Takahiko; Nakano, Shigekazu; Watanabe, Nobuaki; Hirohata, Yoshihide; Ōtsuki, Makoto

doi:10.1097/00006676-199703000-00002

Cited by 23 publications

(11 citation statements)

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“…22 On the other hand, acute pancreatitis develops in the sodium taurocholate-induced pancreatitis model, the CDL-induced pancreatitis model, and the arginineinduced pancreatitis model. 23 It has been reported that the OLETF rats have less severe pancreatitis than the LETO rats. 23 We used ethionine-induced pancreatitis as a model of acute necrotizing pancreatitis.…”

Section: Discussionmentioning

confidence: 98%

“…23 It has been reported that the OLETF rats have less severe pancreatitis than the LETO rats. 23 We used ethionine-induced pancreatitis as a model of acute necrotizing pancreatitis. In ethionineand cerulein-induced pancreatitis, the mechanism is thought to be autodigestion due to a defect in secretion of zymogen granules and the subsequent fusion of zymogen granules and lysosomes in the cytoplasm (autophagy).…”

Section: Discussionmentioning

confidence: 98%

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Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression

Sato

Niikawa

Usui

et al. 2003

Journal of Gastroenterology

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression

Sato

Niikawa

Usui

et al. 2003

Journal of Gastroenterology

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“…It seems therefore appropriate to assume that CCK receptor antagonists can play a therapeutic role. Studies have shown positive effects of CCK antagonists in fi ve different animal models: cerulein-induced pancreatitis, hemorrhagic pancreatitis induced by choline-defi cient diet, ethionine-supplemented diet, arginine-induced pancreatitis and sodium taurocholate-induced pancreatitis [51][52][53] . The role of CCK antagonists has been questioned by de Dios et al [54] who documented that the CCK 1 antagonist L-364,718 failed to show any benefi t and was even harmful in the rat model that they had studied.…”

Section: Pancreatitismentioning

confidence: 99%

CCK<sub>1</sub> Antagonists: Are They Ready for Clinical Use?

Peter

D’Amato²,

Beglinger

2006

Dig Dis

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Cholecystokinin (CCK) is a peptide hormone which is found both in the gastrointestinal tract throughout the human small intestine and nerves in the myenteric plexus of the enteric nervous system and in the central nervous system. This dual location constitutes the anatomical basis for this in functions as a hormone and a neurotransmitter implicated in the regulation of both systems. CCK regulates not only motor functions in the gastrointestinal tract like lower oesophageal sphincter relaxation, gastric secretion and emptying, gall bladder contractility and bile secretion into the duodenum, intestinal and colonic motility, but also sensory functions and plays a role in the regulation of food intake. These effects are mediated through selective receptors CCK₁ and CCK₂. Over the last few years, research has focused on understanding the role of CCK, its receptors with antagonists at the biological, pharmacological, clinical and therapeutic level. As far as the CCK₁ antagonists is concerned, important inroads have been made in the potential role of these antagonists in the treatment of GERD, IBS and pancreatitis. They have also shown encouraging results in sphincter of Oddi dysfunction and some gastrointestinal cancers. This review focuses on the recent ad vances of the biological role of CCK and their CCK₁ antagonists: their current basic and clinical status in gastroenterology, with particular emphasis on the potential therapeutic role of the CCK₁ antagonists and future research directions.

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“…Particularly puzzling is the observation that, while CCK-8 and bombesin both stimulate protein secretion by mobilizing intracellular calcium and both strongly stimulate pancreatic enzyme secretion, supraphysiological doses of bombesin do not cause pancreatitis or inhibit pancreatic secretion (12,44). Also unexplained is the observation that prolonged unphysiologically high levels of endogenous CCK do not induce pancreatitis in rats (28,34), nor do high endogenous CCK levels exacerbate experimental pancreatitis after it is initiated (18,29,37,39,42). We recently reported that CCK-58 is the only detectable endocrine form of CCK in the rat (32) and the most abundant endocrine form of CCK in humans (7) and dogs (9).…”

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confidence: 99%

Supramaximal CCK-58 does not induce pancreatitis in the rat: role of pancreatic water secretion

Yamamoto

Reeve²,

Green³

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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In contrast to supramaximal CCK-8 or caerulein, acute or prolonged supraphysiological levels of endogenous CCK-58 do not cause pancreatitis. Compared with CCK-8, CCK-58 is a much stronger stimulant of pancreatic chloride and water secretion, equivalent to maximally effective secretin, but with a chloride-to-bicarbonate ratio characteristic of acinar fluid. Because supraphysiological endogenous CCK does not cause pancreatitis and because coadministration of secretin ameliorated caerulein- or CCK-8-induced pancreatitis, coincident with restoring pancreatic water secretion, we hypothesized that supramaximal CCK-58 would not induce pancreatitis. Conscious rats were infused intravenously with 2 or 4 nmol x kg(-1) x h(-1) of CCK-8 or synthetic rat CCK-58 for 6 h, and pancreases were examined for morphological and biochemical indexes of acute pancreatitis. A second group was treated as above while monitoring pancreatic protein and water secretion. CCK-8 at 2 nmol x kg(-1) x h(-1) caused severe edematous pancreatitis as evidenced by morphological and biochemical criteria. CCK-58 at this dose had minimal or no effect on these indexes. CCK-58 at 4 nmol x kg(-1) x h(-1) increased some indexes of pancreatic damage but less than either the 2 or 4 nmol x kg(-1) x h(-1) dose of CCK-8. Pancreatic water and protein secretion were nearly or completely abolished within 3 h of onset of CCK-8 infusion, whereas water and protein secretion were maintained near basal levels in CCK-58-treated rats. We hypothesize that supramaximal CCK-58 does not induce pancreatitis because it maintains pancreatic acinar chloride and water secretion, which are essential for exocytosis of activated zymogens. We conclude that CCK-58 may be a valuable tool for investigating events that trigger pancreatitis.

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Role of Endogenous Cholecystokinin and Cholecystokinin-A Receptors in the Development of Acute Pancreatitis in Rats

Cited by 23 publications

References 0 publications

Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression

Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression

CCK<sub>1</sub> Antagonists: Are They Ready for Clinical Use?

Supramaximal CCK-58 does not induce pancreatitis in the rat: role of pancreatic water secretion

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