Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow

Konturek, Stanisław J.; Bilski, Jan; Konturek, P C; Cieszkowski, Marek; Pawlik, Wiesław W.

doi:10.1016/0016-5085(93)91028-g

Cited by 82 publications

(64 citation statements)

References 13 publications

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“…Furthermore, neuronal and vascular endothelial cells (12,14), which are present in close proximity to pancreatic acinar cells, can also contribute to the increased levels of reactive oxygen and nitrogen species. Further support for our hypothesis that nitrosative stress is a possible mediator for L-arginine-induced pancreatitis comes from our data indicating that similar concentrations of D-arginine (stereoisomer for L-arginine) and other amino acids, which are not substrates for NOS, do not cause pancreatic damage.…”

Section: Discussionmentioning

confidence: 99%

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Dawra

Sharif

Phillips

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

163

131

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Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol 292: G1009 -G1018, 2007. First published December 14, 2006; doi:10.1152/ajpgi.00167.2006.-The pathogenesis of acute pancreatitis is not fully understood. Experimental animal models that mimic human disease are essential to better understand the pathophysiology of the disease and to evaluate potential therapeutic agents. Given that the mouse genome is known completely and that a large number of strains with various genetic deletions are available, it is advantageous to have multiple reliable mouse models of acute pancreatitis. Presently, there is only one predominant model of acute pancreatitis in mice, in which hyperstimulatory doses of cholecystokinin or its analog caerulein are administered. Therefore, the aim of this study was to develop another mouse model of acute pancreatitis. In this study, C57BL/6 mice were injected intraperitoneally with L-arginine in two doses of 4 g/kg each, 1 h apart. Serum amylase, myeloperoxidase, and histopathology were examined at varying time points after injection to assess injury to the pancreas and lung. We found that injection of L-arginine was followed by significant increases in plasma amylase and pancreatic myeloperoxidase accompanied by marked histopathological changes. The injury to the pancreas was slow to develop and peaked at 72 h. Subsequent to peak injury, the damaged areas contained collagen fibers as assessed by increased Sirius red staining. In contrast, D-arginine or other amino acids did not cause injury to the pancreas. In addition, acute inflammation in the pancreas was associated with lung injury. Our results indicate that administration of L-arginine to mice results in severe acute pancreatitis. This model should help in elucidating the pathophysiology of pancreatitis.pancreas; lung injury; fibrosis ACUTE PANCREATITIS IS AN INFLAMMATORY disease of the pancreas resulting in significant morbidity and mortality (13). Various causes, including gallstones, alcohol, trauma, infections, and genetic alterations, have been implicated in the causation of this disease (1, 23). Although our understanding of the cell biology of the exocrine pancreas and epidemiology of pancreatitis has increased greatly in recent years, our knowledge of its pathophysiology and the ability to prevent or treat pancreatitis remain limited (23). This can partially be attributed to the paucity of clinical material from the early stages of the disease available for research. To overcome this and to study the effect of new therapeutic agents, different experimental animal models of pancreatitis have been developed. Our present limited understanding about the events associated with the development of the disease is based on the use of these experimental models (21). Among the animals used for developing experimental models, the mouse is ideal because of the availability of several genetic man...

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Section: Discussionmentioning

confidence: 99%

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Dawra

Sharif

Phillips

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

163

131

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“…Konturek et al (1993) were the first to demonstrate in fistulated dogs, with pancreatic blood flow measured by laser Doppler flowmetry, that endogenous NO affects pancreatic secretion through the changes in the vascular bed. They found that besides sham-feeding and meal feeding, continuous infusions of secretin plus CCK markedly induced pancreatic protein outputs.…”

Section: Local Effects Of Cholecystokinin and Gastrin In The Gutmentioning

confidence: 99%

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

et al. 2006

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The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK 1 and CCK 2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

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“…As a result, outputs of amylase and bile juice were not increased. This idea is drawn from the relationship between the nutrient amount passing into the duodenum and some hormones, CCK and secretin, at the intestinal phase but not the cephalic phase, since amylase output is also increased at the shamfeeding state (cephalic phase) [15]. However, this theory may not fully explain our observations in this study.…”

Section: Discussionmentioning

confidence: 79%

“…As we did not measure hemodynamic parameters as part of our experimental protocol, this explanation is speculative. Regarding the pancreas, Konturek et al [15] suggest that the decrease in amylase release after the administration of NO synthase inhibitor is due to a decrease of blood flow to the pancreas. It is considered that NO is an endothelium-derived relaxing factor (EDRF) [25] and mediates the action of some vasodilators.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of NO on pancreaticobiliary secretion has also been reported. Konturek et al [14,15] demonstrated that the NO inhibits exocrine pancreatic secretion in both fasting and fed states in dogs. Mourelle et al suggested that the NO modulates gallbladder contractions [20] and the sphincter of Oddi [21] in both fasting and CCK-induced contractile states in guinea pigs and rabbits.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Nitric Oxide Synthase Inhibitor on the Digestive System Measured by Simultaneous Monitoring of Gastric Motility, Gastric Emptying Activity and Postprandial Pancreaticobiliary Secretion in Dogs

Tanaka

Mizumoto

2005

Exp. Anim.

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Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow

Cited by 82 publications

References 13 publications

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

Effects of Nitric Oxide Synthase Inhibitor on the Digestive System Measured by Simultaneous Monitoring of Gastric Motility, Gastric Emptying Activity and Postprandial Pancreaticobiliary Secretion in Dogs

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