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P Chowdhury

Publications and source records attributed to P Chowdhury.

At least 19 recordsLinked to original sources
PubMed1995

Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic acinar cells.

Nicotine is a possible risk factor for chronic pancreatitis and pancreatic cancer. To study the loci where nicotine might exert its effect, we examined interactions between nicotine and rat pancreatic acini. When pancreatic acini were incubated with [3H]nicotine, [3H]nicotine levels in pancreatic acini were increased in time-and dose-dependent manners, and the t1/2 for dissociation of [3H]nicotine was 63.8 min. At 4 degrees C, the association of [3H]nicotine was 33% of the association at 37 degrees C. Unlabeled nicotine had no significant effect on the accumulation of [3H]nicotine. In addition, surface-bound [3H]nicotine was not detected when acini were washed in a low-pH solution or when they were trypsinized. These results suggest that the accumulation of nicotine may be a biological phenomenon and that [3H]nicotine does not bind to surface receptors of acinar cells, but accumulates intracellularly. The addition of verapamil (0.1 mM) or 12-O-tetradecanoylphorbol-13-acetate (1 microM) had no effect on [3H]nicotine association, while 4-bromo-A23187 (2 microM) or EGTA (10 mM) significantly increased the accumulation of [3H]nicotine. Carbachol and cholecystokinin significantly enhanced the accumulation of [3H]nicotine in a dose-dependent manner. Taken together, the increasing effects of carbachol and cholecystokinin on the accumulation of nicotine may explain, at least in part, the mechanisms involved in the multiplicative effects of the combination of two risk factors, smoking habit and high-fat or high-protein diets, on human pancreatic diseases.

Animals↗
PubMed1993

Agonist-regulated alteration of the affinity of pancreatic muscarinic cholinergic receptors.

Heterologous desensitization is a term that indicates that exposure of a cell to an agonist attenuates the response of that cell to other agonists. We examined heterologous desensitization of muscarinic cholinergic receptors of pancreatic acini and characterized mechanisms that might be responsible for desensitization. Muscarinic cholinergic receptor binding was measured by using N-[3H]methscopolamine bromide ([3H]NMS). N-Methscopolamine bromide (NMS), a receptor antagonist, bound to a single class of receptors with an affinity of 0.22 +/- 0.04 nM and a capacity of 61.5 +/- 5.1 fmol/mg of protein. These parameters of NMS binding sites were not altered by an addition of cholecystokinin (CCK) octapeptide, CCK-JMV-180, vasoactive intestinal peptide, 8-bromo-cAMP, 4-bromo-A23187, thapsigargin, or 12-O-tetradecanoylphorbol-13-acetate (TPA). Analysis of competitive inhibition curve of [3H] NMS binding by carbachol showed apparently two classes of carbachol binding sites with high affinity (38.6%) and low affinity (61.4%). Simultaneous incubation of carbachol with CCK or TPA increased the relative affinity of [3H]NMS binding, and the competitive inhibition curves showed a single class of carbachol binding site. L-364,718 blocked the effect of CCK, and staurosporine blocked the effects of TPA and partially blocked the effect of CCK. CCK-JMV-180, vasoactive intestinal peptide, 8-bromo-cAMP, 4-bromo-A23187, and thapsigargin had no effects on the competitive binding. Second, the carbachol-induced sequestration of the receptors was examined. Incubation of acini with carbachol resulted in a decrease of [3H] NMS binding sites, and the addition of CCK or TPA caused an inhibition of the carbachol-induced disappearance of [3H]NMS binding sites. Finally, studies that examined the biological response of the acinar cells showed that biphasic amylase release in response to carbachol was completely suppressed by 10 nM CCK for entire range of carbachol. Taken together, these results suggest that the effect of CCK on carbachol-induced sequestration is important for the alteration of the apparent affinity of carbachol binding sites and the biological response of acinar cells to carbachol. Further, the results suggest that another factor that induces uncoupling of receptor from effector might be involved in agonist-regulated desensitization. The results, that CCK-JMV-180 or other agonists that activate the adenylate cyclase pathway did not exert these effects of CCK, suggest that protein kinase C may be one of the key factors involved in heterologous desensitization by CCK on the carbachol binding sites and the suppression of carbachol-induced amylase release.

Amylases↗
PubMed1993

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.

Animals↗
PubMed1993

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

Effects 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 microgram/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 micrograms/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.

Amino Acids↗
PubMed1993

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

This 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.

Amylases↗
PubMed1993

Structural and functional changes of exocrine pancreas induced by FK506 in rats.

BACKGROUND: The pancreas has been reported as a possible target for FK506 toxicity. This study was conducted to examine the effects of FK506 on the structure and function of pancreatic acinar cells. METHODS: Male Sprague-Dawley rats received an intramuscular injection of saline or FK506, and pancreatic acini were isolated on the day of sacrifice. RESULTS: FK506 caused a time-dependent suppression in amylase secretory response to cholecystokinin or carbachol at days 3-14, and increases in amylase and trypsinogen content at days 7-14. The properties of cholecystokinin and scopolamine binding sites in acini were not altered by FK506. Amylase release by A23187 and secretin were decreased by FK506, but those by phorbol ester 12-O-tetradecanoylphorbol-13-acetate, forskolin, 5'-cyclic adenosine monophosphate and vasoactive intestinal peptide were not changed. Increases in cytosolic free calcium concentration induced by cholecystokinin were not changed by FK506. Histologically, a significant increase in cytoplasmic zymogen granules was observed in pancreas from FK506-treated rats. CONCLUSION: These data suggest that FK506 induced changes in function and metabolism in pancreatic acinar cells, and these changes might be caused by altering postreceptor loci in stimulus-secretion coupling.

Amylases↗
PubMed1993

Humoral factors that induce alterations of the pancreas in rats with obstructive jaundice.

This study was conducted to investigate the role of humoral factors in pancreatic alterations induced by obstructive jaundice (OJ) in rats. OJ in male Sprague-Dawley rats induced significant increases in pancreatic weight, DNA content, and RNA content of acinar cells. These changes were accompanied by enlargement of eosinophilic granules and compressed nuclei. Protein, amylase, and trypsinogen contents of pancreas were also increased in OJ rats. In addition, plasma levels of bilirubin, cholecystokinin (CCK), and estradiol increased in OJ rats and were correlated positively with each other and with pancreatic weights. Administration of a specific CCK receptor, L-364,718, to OJ rats partly attenuated the changes of the pancreas, indicating that CCK is involved in these changes. These findings suggest that estradiol may be involved in regulating the pancreatic changes induced by OJ in rats.

Amylases↗
PubMed1993

Retrieval and amplification of DNA from unstained histopathological sections.

Testing of compounds for carcinogenic potential in vivo involves various experimental designs. A few of these techniques are directed to demonstrate the genotoxicity and mutagenicity of the compound by histopathology. These changes shown by histochemical means include monoclonal antibody directed cellular markers. Development of the polymerase chain reaction technique (PCR) for amplification of DNA has facilitated the investigation of molecular events related to the formation of malignant neoplasms. We describe here a method for screening tissues for mutations of the H-ras gene using monoclonal antibodies directed toward normal and mutant p21 proteins. Formalin-fixed, paraffin-embedded tissue sections are used to subsequently confirm the gene mutation by PCR amplification of the H-ras gene. The results indicated a successful application of this technique to demonstrate the presence of p21 oncoprotein in the tissues tested.

Antibodies, Monoclonal↗
PubMed1993

Biochemical characterization of the effects of FK506 on signal transduction in exocytotic function of rat pancreatic acini.

We examined the effects of FK506 on amylase secretion and intracellular pathway in stimulus secretion coupling in isolated pancreatic acini. Amylase release from isolated acini in response to cholecystokinin octapeptide (CCK-8) was suppressed by exposing acini to FK506. The suppressing effect of FK506 on amylase release from acini was dependent on the concentration of FK506 and the time of exposure to FK506. Amylase releases in response to 8-bromo-cAMP and vasoactive intestinal peptide and phorbol ester (12-O-tetradecanoylphorbol 13-acetate) were not suppressed when acini were exposed to FK506, suggesting that the cAMP-dependent protein kinase pathway and protein kinase C pathway were not affected by FK506. However, amylase release in response to calcium ionophore (4-bromo-A23187) was suppressed by FK506, whereas the increase in cytosolic free calcium concentration caused by 4-bromo-A23187 was not affected by FK506. These results suggest that FK506 suppressed secretagogue-stimulated amylase release in acini by altering Ca(++)-mediated intracellular pathways. Further, the property of CCK-8 binding site, CCK-8 stimulated inositol phosphates formation, rises in cytosolic free calcium concentration, and calcium efflux from acini were not suppressed by exposing acini to FK506. These findings indicate that FK506 suppresses amylase release by affecting postreceptor intracellular pathways that are mediated by Ca++ in stimulus secretion coupling.

Amylases↗
PubMed1993

The influence of vagotomy on basal and postprandial pancreatic secretion and plasma levels of gastrointestinal hormones in conscious rats.

This study was conducted to investigate the effect of vagotomy on basal and postprandial pancreatic secretion and plasma levels of gastrointestinal hormones. Thirteen rats underwent vagotomy and 12 underwent sham operation. All of the rats were prepared with gastric and pancreatic fistulas. Before and after an intragastric infusion of liquid meal, pancreatic fluid and protein outputs and plasma levels of cholecystokinin and gastrin were measured. Vagotomy induced a delay and a decrease in postprandial responses in pancreatic volume and protein outputs. Vagotomy had no effect on basal and postprandial plasma levels of cholecystokinin. Basal and postprandial levels of plasma gastrin were significantly increased after vagotomy, but the postprandial patterns of gastrin release were not significantly different between the two groups. Vagal regulation may be important in the basal gastrin release but is not involved in basal release of cholecystokinin or postprandial releases of gastrin and cholecystokinin. The current results indicate that vagotomy influences postprandial pancreatic secretion. This effect is probably the result of interrupted vagus-mediated reflexes between the intestinal tract and the pancreas.

Animals↗
PubMed1992

Characterization of interactions between CCK-33 and CCK receptors in isolated dispersed pancreatic acini.

In isolated dispersed pancreatic acini, we have characterized the interactions between cholecystokinin (CCK) and CCK receptors by simultaneously measuring CCK-33 immunoreactivity and CCK bioactivity. Incubation of acinar cells with CCK-33 at cell density of 0.2-0.3 mg acinar protein per ml resulted in stimulation of amylase release concomitant with significant and time-dependent decrease of the immunoreactive CCK. With L-364,718 (0.1 microM), a specific CCK receptor antagonist, immunoreactive CCK levels in the media were not significantly altered during incubation; however, CCK-stimulated amylase release was almost completely abolished (94% inhibition). Vasoactive intestinal peptide (1 nM) significantly potentiated CCK stimulated amylase release without affecting immunoreactive CCK in the media. Insulin (167 nM) did not affect the CCK stimulated amylase release or immunoreactive CCK in the media. Incubation of acinar cells with CCK-33 at 4 degrees C did not affect the levels of immunoreactive CCK; however, a significant change in levels of immunoreactive CCK were found at 37 degrees C at 90 min. Incubation of cell free medium with CCK-33 in the presence or absence of secreted enzymes revealed no changes in CCK immunoreactivity in the medium at 90 min. Addition of bacitracin in the incubation media did not affect the CCK immunoreactivity or bioactivity. These findings indicate that in isolated rat pancreatic acini, CCK-33 stimulates amylase release through a receptor that is specifically blocked by L-364,718. Specificity of the interactions of CCK-33 with acinar cells in the media appears to be receptor-mediated and time- and temperature-dependent.

Amylases↗
PubMed1992

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.

Amylases↗
PubMed1992

Effects of FK506 on exocrine pancreas in rats.

The efficacy of FK506 on exocrine pancreas was studied in rats. Male Sprague-Dawley rats (230-250 g) received an i.m. daily injection of FK506 (0.1, 0.5, or 5.0 mg/kg), cyclosporine (CS; 25 mg/kg), or saline for 2 weeks. Isolated dispersed pancreatic acini were prepared from rats, and enzyme content of the cells and secretory response to cholecystokinin (CCK) were determined. Amylase and trypsin contents were increased in a dose-related manner by FK506 (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). The release of amylase in response to CCK was reduced by FK506 in a dose-related manner (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). Histologic examination showed that treatment of rats with FK506 at 0.1 mg/kg did not affect morphology of the acinar cells. FK506 at 0.5 mg/kg induced a minimal number of small vacuoles in cytoplasm of acinar cells and FK506 at 5.0 mg/kg, and CS at 25 mg/kg induced numerous cytoplasmic vacuoles and pyknotic nuclei. Increased enzyme storage and suppressed responsiveness of amylase release may have an association with the histologic changes. Therefore, the results of this study suggest that FK506, even when used in a low dose, may have adverse effects on the exocrine pancreas. Understanding of the mechanism of action of FK506 on pancreas will provide essential basic information that will allow transplant practitioners to more fully explore the benefits of this drug.

Amylases↗
PubMed1992

Pyogenic hepatic abscess and septic pulmonary emboli associated with Klebsiella ozaenae bacteremia.

We have reported a case of cryptogenic liver abscess with bacteremia and septic pulmonary emboli due to Klebsiella ozaenae. This organism has not previously been reported as a cause of intra-abdominal infection and this is only the eighth reported case of bacteremia. K ozaenae is generally considered an opportunist of low virulence and a respiratory tract colonizer implicated in ozena (atrophic rhinitis). More information is required to understand the epidemiology and pathogenicity of human disease caused by K ozaenae.

Aged↗
PubMed1992

Induction of pancreatic acinar pathology via inhalation of nicotine.

This study was conducted to determine the effects of nicotine inhalation on the onset, progression, and sequential development of pancreatic lesions. Male Sprague-Dawley rats in groups of five were exposed to saline or nicotine aerosol twice daily for 15, 30, 45, and 60 min for 21 days. After sacrifice, blood samples were analyzed for plasma levels of nicotine, glucose, gastrin, and cholecystokinin. Pancreatic tissues were examined for pathological lesions. While there were no significant differences in plasma levels of glucose, gastrin, and cholecystokinin in all groups, there was a steady increase in plasma levels of nicotine with increased exposures to nicotine. Histopathological examination of pancreatic tissue revealed definitive pancreatic injuries that also appeared to be directly correlated with increased duration of nicotine exposure. The pathological changes of the pancreas were confined only to acinar cells of the exocrine pancreas. Two main types of cellular changes were observed: cellular swelling/vacuolation and nuclear condensation/cellular pyknosis. Both of these changes indicated tissue injuries in the pancreas. Transformation of the glandular acini to solid masses of epithelial cells was also observed. The results from our present study strongly suggest that the exocrine pancreas is very sensitive and susceptible to nicotine toxicity. Our data further indicate that early morphological changes in the pancreas induced by nicotine may occur without functional or metabolic alterations; however, such changes could occur at a later stage, when tissue and cellular changes become more extensive.

Administration, Inhalation↗
PubMed1992

Simultaneous measurement of cholecystokinin-stimulated amylase release and cholecystokinin receptor binding in rat pancreatic acini.

In the past, isolated-dispersed pancreatic acini have been used to examine either cholecystokinin-stimulated amylase release or pancreatic acinar cholecystokinin receptors. We have developed and validated a method for simultaneous measurement of synthetic cholecystokinin octapeptide-stimulated (CCK8-stimulated) pancreatic amylase release and cholecystokinin receptors. After an 18-hour fast, rats were killed and their pancreatic acini isolated. Three-milliliter aliquots of acinar suspension were incubated for 60 minutes in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-Ringer buffer containing graded doses of CCK8 and a constant amount (7 pmol/L) of iodine 125-labeled CCK8 (by the Bolton-Hunter method) ([125I]BH-CCK8). A 1 ml sample was removed from each flask for determination of amylase release, and the remaining 2 ml were used to determine cholecystokinin receptor capacities and affinities. The median effective dose for amylase release was 16 pmol/L, and release was maximal at 100 pmol/L CCK8 plus 7 pmol/L [125I]BH-CCK8, a dose that released 28% +/- 3% of total cellular amylase content. High affinity (equilibrium dissociation constant of high-affinity receptors = 58 +/- 8 pmol/L, receptor density of high-affinity receptors = 4 +/- 1 fmol/mg protein) and low affinity (equilibrium dissociation constant of low-affinity receptors = 7 +/- 2 nmol/L, receptor density of low-affinity receptors = 313 +/- 108 fmol/mg protein) cholecystokinin receptors were measured. The results demonstrate that CCK8-stimulated amylase release and cholecystokinin receptor binding in pancreatic acini can be measured concurrently and that the parameters of amylase release and cholecystokinin receptor binding are strikingly similar to those previously observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1992

Use of a specific cholecystokinin receptor antagonist (L-364,718) to determine the role of cholecystokinin on feeding and body weight in rats with obstructive jaundice.

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Animals↗