Ryuichiro Doi

Structural and functional changes of rat exocrine pancreas exposed to nicotine

SummaryNicotine, an addictive agent in cigaret smoking, has been implicated in the etiology of pancreatitis and pancreatic carcinoma. Very little experimental data are, however, available regarding the effects of nicotine on the structural and functional changes in the exocrine pancreas. Two groups of rats divided into control and nicotine exposed were used. The animals in the nicotine group were maintained for 28 d with ad libitum water containing 0.77 mM of nicotine. At term, the animals were sacrificed, and pancreas was examined for pathological and functional changes. Nicotine induced cytoplasmic vacuolation and cellular edema in the exocrine pancreas. Plasma levels of glucose and insulin and CCK-8-stimulated amylase release in isolated acini were significantly decreased by nicotine, whereas the total cellular amylase content was significantly increased. Analysis of competitive ligand binding data on membranes from isolated acini showed that theBmax andKd values for CCK receptors were not significantly changed by nicotine,p>0.05. These data indicate that a postreceptor mechanism is involved in the inhibition in stimulus-secretion coupling of enzyme secretion by nicotine. The increase in total cellular amylase content and decreased enzyme secretion by nicotine may be implicated in the induction of pancreatic pathology.

Exogenous administration of estradiol and cholecystokinin alters exocrine pancreatic function in rats

SummaryThis study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.

Tissue distribution of cadmium-109 after tracheal and gastric administration in rats

Cadmium is known to be a toxic trace element and its ingestion into the human body via dietary, inhalation, occupational, or non-occupational sources can induce a variety of pulmonary, renal, or reproductive dysfunction. Many acute and chronic studies with cadmium have been conducted in experimental animals to determine its mechanism of action, and it has been reported that cadmium may enhance or deactivate several enzyme systems in vitro or in vivo, and it may act as a potent calcium blocker, and can inhibit calmodulin activity. In addition, cadmium is distributed and retained in organ systems such as liver, kidney and lung. We have previously shown that a significant amount of cadmium is accumulated in lung, kidney, liver and gastrointestinal tract following intravenous or intraperitoneal injection. This study was conducted to delineate the tissue distribution of cadmium in animals following more physiologic route of exposure, such as tracheal and gastric administration of cadmium. 14 refs., 2 figs.

Exocrine pancreatic function in obstructive jaundice rats: Studies with isolated dispersed pancreatic acini

This study was conducted to investigate pancreatic exocrine function and pancreatic growth in rats with obstructive jaundice (OJ). OJ was produced in adult male Sprague-Dawley rats by bile duct ligation; control rats underwent laparotomy only. Induction of OJ was associated with significant hyperplasia and hypertrophy of the pancreas in rats as shown by increased DNA and RNA contents of pancreatic tissue. Factors associated with pancreatic growth in OJ rats were further examined in isolated dispersed pancreatic acini from OJ rats and the data were compared with those for control rats. Studies with isolated dispersed acini from OJ rats showed that pancreatic growth was accompanied by significant increases in total cellular amylase content; however, amylase release (percentage of initial) in response to cholecystokinin octapeptide was significantly decreased in OJ rats compared to control rats. Total amylase output in response to 100 pM cholecystokinin (CCK) was higher in the OJ group when compared to the control group (8.6 U/mg protein versus 6.4 U/mg protein), as calculated from the total amylase content and percentage of amylase released. Receptor binding data showed that the capacity of CCK receptors in OJ rats was significantly lower when it was compared with control. In addition, plasma levels of CCK were significantly elevated in OJ rats when compared to controls. These results suggest that obstructive jaundice induces pancreatic growth that is associated with alteration of exocrine pancreatic function. Abnormally high levels of stored amylase in pancreatic acini may be implicated in the development of pancreatitis as often seen in obstructive jaundice patients.

The role of gastrointestinal peptides on pancreatic secretion in response to different stimulants in conscious rats

SummaryEffects of intragastric food, intraduodenal amino acids, and intravenously administered bombesin and gastrin-releasing peptide (GRP) were examined in conscious rats with pancreatic fistula in terms of responses of exocrine pancreatic secretion, plasma levels gastrin, and cholecystokinin (CCK). Pancreatic juice and blood samples were collected at regular intervals before and after the stimuli. Intragastric food increased pancreatic secretion and plasma levels of gastrin and CCK. Intraduodenal infusion of amino acids had no effect on pancreatic secretion and plasma levels of gastrin and CCK. Intravenous infusion of bombesin at 1 μg/kg/h induced significant increases in pancreatic volume and protein outputs, but had no effect on plasma levels of gastrin and CCK. Bombesin infusion at 10 μg/kg/h resulted in significant increases in pancreatic volume and protein outputs as well as plasma gastrin levels, but had no effect on plasma CCK levels. Intravenous infusion of GRP induced increases in pancreatic volume and protein outputs and plasma gastrin levels, but had no effect on CCK levels. Antrectomy resulted in significant decreases in basal levels of plasma gastrin. GRP-stimulated pancreatic volume and protein outputs were not significantly changed by antrectomy. In rats that underwent antrectomy, GRP infusion significantly increased pancreatic volume and protein outputs, but had no effect on plasma levels of gastrin and CCK. Food-stimulated pancreatic secretion and plasma levels of gastrointestinal peptides of rats were similar to other species, but amino acids, bombesin, or GRP may not be the stimulants for CCK release in rats. The stimuli that release CCK from duodenal mucosa probably varies among species.

The effect of intravenous cadmium on exocrine and endocrine pancreatic functions in conscious dogs

This study was conducted in conscious dogs to investigate the effect of cadmium on exocrine pancreatic secretion and plasma levels of pancreatic polypeptide (PP). Mongrel dogs weighing 20–25 kg were prepared with chronic gastric and pancreatic fistulas, and were acclimated for 3 wk prior to studies. The dogs were given iv infusion of saline, secretin at 25 U/kg/h, cadmium at 0.15 mg/kg/h, or various combinations of these compounds. During the infusion, pancreatic juice and blood samples were collected at regular intervals. Secretin infusion stimulated pancreatic secretions. Infusion of cadmium alone had no effect on pancreatic secretions and plasma levels of PP. When cadmium infusion was stopped with the background infusion of secretin, pancreatic secretions and plasma levels of PP were significantly increased. This latent effect of cadmium on pancreatic secretions and plasma levels of PP was abolished by an iv injection of 100 mg/kg atropine. These results indicate that cholinergic signaling may be involved in the effect of cadmium on pancreatic exocrine secretions and PP release. The current study suggests that cadmium may have diverse physiological functions in both exocrine and endocrine pancreatic cells.

Near-infrared intraoperative imaging of pancreatic neuroendocrine tumors: a new era in laparoscopic pancreatic surgery

It is evident that safe complete resection of the target tumor without excess or deficiency is the most important object in the oncological surgery, besides this is particularly true in the laparoscopic surgery for pancreatic neuroendocrine tumors (PanNETs).