Pathophysiological effects of nicotine on the pancreas: an update.

Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic diseases. It is well recognized that nicotine, a major component in cigarette smoke, is an addictive agent and, therefore, reinforces smoking behavior. The current review update focuses on the genetics of nicotine dependence and its role on the development of pancreatic diseases.

Alcohol, tobacco (nicotine) and pancreatic pathophysiology.

Current knowledge indicates that chronic use of alcohol is implicated in the etiology of chronic pancreatitis and probably in pancreatic cancer and that chronic use of tobacco is associated with pancreatic cancer and probably pancreatitis. Studies by others, and by us, support this knowledge. In addition, our studies suggest that nicotine, which is a major component and an additive component of tobacco, is probably a major factor in these pathological effects.

Mecamylamine, a nicotinic receptor channel antagonist, affects amylase secretion by isolated pancreatic acinar cells.

It is well established that CCK is a potent stimulator of amylase secretion from the pancreatic acinar cells, while nicotine is an effective inhibitor of such secretion. The present study was conducted to determine whether mecamylamine, a well-established ganglionic blocker drug, could influence amylase secretion from the pancreas. Male Sprague-Dawley rats were fasted, sacrificed, the pancreas removed, and pancreatic acinar cells isolated and purified.

Effect of food restriction on plasma cholecystokinin levels and exocrine pancreatic function in rats.

The objective of this study was to examine the effects of 10% food restriction on body weight, plasma cholecystokinin (CCK) levels, and exocrine pancreatic function in male Sprague-Dawley rats. A matched group of rats with unrestricted access to food served as controls. After ingesting the diets for 32 da, the rats were killed and blood obtained for plasma cholecystokinin, glucose, and insulin determinations.

Smoking and pancreatic disorders.

Cigarette smoking is a major risk factor for pancreatic cancer and probably pancreatitis. It has been reported that patients with chronic pancreatitis are 16 times more likely to develop pancreatic cancer than normal individuals. Nicotine, a major component of tobacco and an addicted drug of abuse in humans, appears to play a role in the aetiology of both pancreatic cancer and pancreatitis.

Response of rat exocrine pancreas to high-fat and high-carbohydrate diets.

Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a highfat diet that contained excess amounts of cottonseed oil or a high-carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas.

Effects of diversion and reperfusion of pancreaticobiliary juice on amylase release from isolated rat pancreas.

Diversion of pancreaticobiliary juice from the small intestine results in resetting of the normal negative-feedback regulation of exocrine pancreatic secretion. The mechanism by which this process occurs is not well understood. To examine this regulatory process, we investigated the effects of pancreaticobiliary juice diversion and reperfusion on exocrine pancreas using isolated rat pancreatic acini.

Structural and functional changes of rat exocrine pancreas exposed to nicotine.

Nicotine, an addictive agent in cigarette 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.

Effects of diet on cholecystokinin-stimulated amylase secretion by pancreatic Acini and amylase mRNA levels in rat pancreas.

To investigate the mechanisms by which dietary compositions regulate the exocrine pancreas, we examined the effects of no-fat diet (NFD) and high-fat diet (HFD) on cholecystokinin (CCK)-stimulated amylase secretion from rat pancreatic acini. Rats were maintained for 4 weeks on NFD or HFD, which contained 0 or 45% fat and 58 or 29% carbohydrates, respectively. Pancreatic acini were isolated and stimulated by graded doses of CCK for 30 min.

Increased plasma levels of pancreatic polypeptide and decreased plasma levels of motilin in encopretic children.

Objective: Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls.

Effect of gamma-irradiation on the effector function of T lymphocytes in microbial control.

A chlamydial-specific T cell clone, capable of inhibiting the growth of infectious Chlamydia in vivo and in vitro, was employed to investigate the effect of gamma-irradiation on the ability of effector T cells to control infections. Clone 2.14-0 (CD4+), specific for the Chlamydia trachomatis biovar agent of mouse pneumonitis (MoPn), was irradiated with varying doses (0, 2.

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.

Gastric pH monitoring after pylorus preserving pancreaticoduodenectomy with Billroth I type of reconstruction.

Background: A late complication of pancreaticoduodenectomy is anastomotic ulcer, and the complication is lessened when pancreaticoduodenectomy is accompanied by preservation of the pylorus. However, the results of some reports suggest that acid levels are not significantly different between patients who undergo pylorus preserving pancreaticoduodenectomy (PPPD) and those having standard pancreaticoduodenectomy. In this study, we measured gastric acidity in the same patients both before and after PPPD.

Metabolism of cholecystokinin-33 in vivo: effect of L-364,718, a CCK receptor antagonist.

Metabolism of cholecystokinin (CCK) and the effect of L-364,718, a specific CCK-A receptor antagonist, on the metabolism of CCK were examined in dogs. In conscious dogs, 45 min intravenous infusion of synthetic human CCK-33 (100 pmol/Kg/hr) caused an integrated CCK response over 90 min of 675 +/- 51 pmol-90 min/L, and the plasma CCK levels declined promptly with a t1/2 of 2.2 +/- 0.

Circadian variations of gastrointestinal peptides and cell proliferation in rats: effects of adrenalectomy.

The hypothalamo-pituitary-adrenal axis appears to play an important role in regulating the circadian fluctuations of brain-gut peptides, as well as the cell cycle of the gastrointestinal mucosa. Since dexamethasone treatment tended to restore circadian fluctuations lost to adren-x, the influence of adrenal glucocorticoids in the coordination of the rhythms of regulatory peptides and cell cycle kinetics appears to be substantial.

Effect of vagotomy on cholecystokinin release and gallbladder contraction in patients with complicated duodenal ulcer.

In this prospective study, we investigated gallbladder (GB) contraction and plasma cholecystokinin (CCK) levels in response to food intake before and 1 month after vagotomy in 27 patients with complicated duodenal ulcer. Highly selective vagotomy (HSV) was carried out in 6 patients, truncal vagotomy and pyloroplasty (TVP) in 4, truncal vagotomy and antrectomy (TVA) in 7, selective vagotomy and pyloroplasty (SVP) in 5 and selective vagotomy and antrectomy (SVA) in another 5 patients with pyloric stenosis. The results of our studies indicated that (1) basal plasma CCK levels increased significantly after vagotomy, (2) none of the vagotomy operations altered the integrated CCK response, (3) unlike HSV, SVA and TVA, SVP and TVP decreased GB emptying and (4) antrectomy significantly enhanced CCK release after food intake.

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.

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.

Alteration in gastrointestinal peptides after thermal injury in humans.

Alterations in gastrointestinal function are common after thermal injury in humans. The peptide hormones gastrin and cholecystokinin are known to exert effects on gastric and biliary motility and on secretory function and to induce trophic changes in gut mucosa. The effect of injury on these hormones has received little attention.

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).

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.

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.