Control Of Exocrine Pancreatic Secretion Research Articles

Neurohormonal control of exocrine pancreatic secretion

Investigations into the neural and hormonal control of pancreatic exocrine function have led to many exciting discoveries over the past year. This review seeks to identify those articles that further our understanding into the complex relation of the varying factors regulating pancreatic secretion. Major findings include the new insights into the regulation of the pancreas through receptor-mediated mechanisms, investigations of pancreatic exocytosis, impairment of pancreatic exocrine function by insulin deficiency, the effects of surgical interventions for the treatment of chronic pancreatitis on pancreatic exocrine function, how exocrine function is altered by the cause of acute pancreatitis, and clinical observations relating to management of pancreatic disease and investigations of pancreatic function testing. Over the past year, substantial new information has been published on the neurohormonal control of pancreatic exocrine function. These data provide insights into the physiology and pathophysiology of pancreatic secretion and diseases of exocrine insufficiency.

Neurohumoral control of exocrine pancreatic secretion

Advancing knowledge about normal physiology of the exocrine pancreas is essential for investigations into the mechanisms of disorders of the pancreas. To this end, reports published during the past year give further insights into the complexity of the hormonal and neural interactions and processes involved in exocrine pancreatic physiology. Key findings include demonstrations of different biologic effects of cholecystokinin peptides on pancreatic secretion, underlining the importance of measurement techniques to determine specific forms of peptide hormones involved in physiologic processes; investigations of the details of the central neural pathways involved in the vago-vagal reflex in pancreatic secretion; the demonstration of the essential role for intrapancreatic nerves in mediating meal-induced responses; and identification of a modulatory role for leptin in exocrine pancreatic secretion. These findings should not only spur further investigations into mechanisms of normal physiology but also provide impetus for application of these findings to studies of pancreatic disorders.

Neurohumoral control of exocrine pancreatic secretion

Reports over the past year provide significant advances in our knowledge of the neurohumoral control of exocrine pancreatic secretion, especially related to human physiology. Major findings include those demonstrating that human pancreatic acinar cells do not respond to cholecystokinin stimulation and that a major circulating form of cholecystokinin is CCK-58. These findings establish that in humans, cholecystokinin causes pancreatic secretion via a neural circuit after interacting with neural sensory receptors in the mucosa of the intestine and that CCK-58 is the likely form of cholecystokinin that stimulates the neural pathways. Other findings demonstrate significant differences in the pancreatic secretory response in humans as a function of the type of nutrient delivered to the gut, especially the fact the elemental diets and medium-chain triglycerides cause much less stimulation of pancreatic secretion than do complex diets. Finally, convincing evidence demonstrating that pancreatic proteases cause inhibition of pancreatic secretion in humans has been presented. In addition to new insights into the neurohumoral control of pancreatic secretion, these findings provide information relevant to both the pathogenesis of pancreatic disorders and their treatment.

Nitric oxide and the pancreas: morphological base and role in the control of the exocrine pancreatic secretion.

The distribution of nitric oxide synthase in both neuronal and non-neuronal pancreatic tissues and the role of nitric oxide in the control of exocrine pancreatic secretion are reviewed in this article. Earlier reports based on in vivo studies suggested that nitric oxide can affect the secretory activity of the exocrine pancreas through changes in pancreatic blood flow. More recently, the employment of either nitric oxide synthase inhibitors or nitric oxide donors in in vitro preparations has provided evidence that nitric oxide can exert a direct action on this gland independently on its vascular effects. Most research in this area seems to indicate that modulation of exocrine pancreatic function by nitric oxide is exerted via activation of guanylate cyclase and generation of cGMP, although other pathways cannot be excluded. Experiments performed over the last year in our laboratory reveal a novel and interesting mechanism based on the ability of nitric oxide to control the release of endogenous neurotransmitter in the pancreas and, subsequently, the nerve-mediated enzyme secretion.

Effect of exogenous insulin and glucagon on exocrine pancreatic secretion in rats in vivo.

The physiological roles of the islet hormones insulin and glucagon in the control of exocrine pancreatic secretion is not clear. It is still unknown whether these hormones have a stimulatory or an inhibitory effect on the basal exocrine pancreatic secretion. Thirty anesthetized rats were stimulated with doses of insulin and glucagon administered by continuous intravenous infusion. Doses varying from physiological to supraphysiological were used. Different groups of 5 rats were given each of these doses. The volume of pancreatic juice and amylase, lipase and trypsin activity, as well as enzyme output, were measured 0, 20, 40, and 60 min after starting infusion. The insulin, glucagon, and glucose levels were determined in serum at 0, 10, 30, and 60 min. In the insulin group, the secreted volume of pancreatic juice increases with the maximum dose. All insulin doses results in amylase and lipase decreased activity. When submaximum and maximum insulin doses are administered, the trypsin activity also decreases. In the glucagon group, the activity of lipase and trypsin decreases regardless the dose, whereas the amylase activity decreases with submaximum and supramaximum doses. Both insulin and glucagon affect the basal exocrine pancreatic secretion in vivo when physiological doses are administered.

Control of exocrine secretion in the guinea-pig pancreas by histamine H3receptors

The aim of this study was to investigate the possible involvement of the histamine H3 receptor in control of exocrine pancreatic secretion from the guinea-pig. In in vitro experiments, the H3 receptor agonist (R)-alpha-methylhistamine (0.01-10 microM) elicited a concentration-dependent decrease in the release of alpha-amylase. (R)-alpha-Methylhistamine concentrations above 10 microM evoked a concentration-dependent increase in alpha-amylase secretion. Application of mepyramine (1 microM) partially blocked this increase. The H3 receptor antagonist thioperanide (1 microM) blocked the effects of (R)-alpha-methylhistamine below 10 microM. Histamine and (R)-alpha-methylhistamine attenuated both protein release elicited during electrical-field stimulation and the release of tritiated choline, and these effects were reversed by thioperamide. In an in vivo study, (R)-alpha-methylhistamine increased juice secretion and total protein content of the juice by 40%. Histamine H1 and H2 receptor antagonists blocked this increase and uncovered an attenuation of the secretory parameters (juice flow 28%, total protein content 44%). This attenuation was blocked by thioperamide. These observations suggest that stimulation of the histamine H3 receptor in the pancreas results in a decreased fluid and enzyme release by inhibition of acetylcholine release from intrinsic pancreatic nerves.

Control of exocrine secretion in the guinea-pig pancreas by histamine H<SUB>3</SUB>receptors

The aim of this study was to investigate the possible involvement of the histamine H3 receptor in control of exocrine pancreatic secretion from the guinea-pig. In in vitro experiments, the H3 receptor agonist (R)-alpha-methylhistamine (0.01-10 microM) elicited a concentration-dependent decrease in the release of alpha-amylase. (R)-alpha-Methylhistamine concentrations above 10 microM evoked a concentration-dependent increase in alpha-amylase secretion. Application of mepyramine (1 microM) partially blocked this increase. The H3 receptor antagonist thioperanide (1 microM) blocked the effects of (R)-alpha-methylhistamine below 10 microM. Histamine and (R)-alpha-methylhistamine attenuated both protein release elicited during electrical-field stimulation and the release of tritiated choline, and these effects were reversed by thioperamide. In an in vivo study, (R)-alpha-methylhistamine increased juice secretion and total protein content of the juice by 40%. Histamine H1 and H2 receptor antagonists blocked this increase and uncovered an attenuation of the secretory parameters (juice flow 28%, total protein content 44%). This attenuation was blocked by thioperamide. These observations suggest that stimulation of the histamine H3 receptor in the pancreas results in a decreased fluid and enzyme release by inhibition of acetylcholine release from intrinsic pancreatic nerves.

Cholinergic Pathways Are Involved in Secretin and VIP Release and the Exocrine Pancreatic Response After Intraduodenally Perfused Acetic and Lactic Acids in the Rat

The response of the exocrine pancreas to intraduodenal perfusion of acetic and lactic acids in normal and previously atropinized rats was studied. Secretin and vasoactive intestinal peptide (VIP) plasma levels in portal plasma were also measured. Intraduodenal perfusion of both acetic and lactic acids significantly stimulated flow rate (from 0.29 +/- 0.03 microliters/min to a maximum of 1.06 +/- 0.08 microliters/min after acetic and from 0.35 +/- 0.05 microliters/min to a maximum of 1.13 +/- 0.12 microliters/min after lactic acid perfusion) and protein output (from 11.16 +/- 2.33 micrograms/min to a maximum of 35.1 +/- 7.4 micrograms/min after acetic and from 8.98 +/- 0.95 micrograms/min to a maximum of 22.5 +/- 1.3 micrograms/min after lactic acid perfusion). Atropine treatment significantly inhibited pancreatic flow rate and protein output after acetic acid perfusion, but no inhibition of flow rate and a slight decrease in the protein output after lactic acid perfusion were seen. With respect to plasma peptide concentrations, significant increases in secretin and VIP levels were found after perfusion of both organic acids; atropine administration significantly decreased plasma secretin levels after acetic acid administration although it did not affect plasma VIP concentrations. By contrast, atropine significantly increased plasma secretin levels, but significantly lower values of plasma VIP concentrations were observed after lactic acid perfusion. Therefore, cholinergic mechanisms are involved in the release of secretin and VIP and different types of control of exocrine pancreatic secretion occur, depending on the features of the intraduodenal stimulant.

Negative Feedback Control of Exocrine Pancreatic Secretion: Role of Cholecystokinin and Cholinergic Pathway

Mediation of postprandial pancreatic enzyme secretion has been ascribed mainly to cholecystokinin and to vagovagal reflexes. Recent studies suggest that these pathways are subject to feedback regulation. Diversion of pancreatic juice from the duodenum stimulates cholecystokinin release and pancreatic enzyme secretion, and intraduodenal administration of trypsin or chymotrypsin inhibits cholecystokinin release and pancreatic secretion. The increased plasma cholecystokinin levels following diversion of pancreatic juice seems to be mediated by "cholecystokinin-releasing factor", a trypsin-sensitive substance secreted by the proximal small intestine. This factor may mediate pancreatic enzyme secretion in response to protein intake. Dietary protein in the intestine competes for the trypsin that would otherwise inactivate the factor. The resulting increase of this factor in the intestinal lumen releases cholecystokinin and stimulates pancreatic enzyme secretion. Enteropancreatic reflex can also be activated by distension or administration of hyperosmolar solutions in the duodenum eliciting pancreatic enzyme secretion without raising plasma cholecystokinin levels. This effect is inhibited by atropine, suggesting that it is cholinergically mediated. Pancreatic response to duodenal volume or osmolality is not suppressed by trypsin, indicating that the reflex is not affected by intraluminal proteases. Our studies also show that secretion of pancreatic polypeptide is under cholinergic control, and this peptide acts by interfering with cholinergic transmission, making it an ideal candidate to modulate pancreatic secretion stimulated by the vagal cholinergic pathway. Similar observations are made with somatostatin and calcitonin-gene related peptide which also acts preferentially to inhibit pancreatic secretion by the vagal cholinergic pathway.

Cholinergic hypothesis of alcoholic pancreatitis.

Chronic alcohol intake interferes especially with the two main pathways regulating exocrine pancreatic secretion: the cholinergic and the pancreozymin pathway. Recently, a new theory of the pathogenesis of alcoholic pancreatitis was proposed emphasizing disordered agonist-receptor interaction at the level of pancreatic acinar cells. Accordingly, alcohol-induced alterations in the control of exocrine pancreatic secretion result in hyperstimulation of pancreatic acinar cells and their muscarinic receptors, mimicking the mechanism of acute pancreatitis caused by scorpion sting, intoxication with an anti-acetylcholinesterase-containing insecticide or supramaximal doses of secretagogues. The present review emphasizes the role of these alcohol-induced secretory alterations in the pathogenesis of alcoholic pancreatitis.

Short-term (8-day) effects of a raw soybean diet on exocrine pancreatic secretion and plasma gastrointestinal hormone levels in the pig.

The aim of the present study was to investigate the short-term (8-day) effects of feeding a raw soybean diet on exocrine pancreatic secretion and the plasma levels of gastrointestinal hormones in pigs. After adaptation to a heated soybean diet, 6 pigs (36.5 +/- 0.8 kg) were fitted with permanent fistulae of the pancreatic duct, the duodenum and a carotid artery. After post-surgical recovery of 8 days, the animals were submitted to two experimental periods, a 4-day period during which they were fed the heated soybean diet and an 8-day period during which they received the raw soybean diet. Exocrine pancreatic secretion and plasma levels of secretin, cholecystokinin, VIP, PP, somatostatin and gastrin were monitored each day of the two experimental periods. On the first day of raw soybean ingestion and till its end, the daily volume of pancreatic juice was higher than the mean volume measured during heated soybean ingestion. On the contrary, daily total protein output was unchanged. Specific activities of chymotrypsin, amylase and lipase were not modified by the raw soybean diet whereas, from the third day of the experimental period, that of trypsin was higher than the corresponding mean value determined during the first experimental period. Plasma levels of secretin and VIP were higher throughout raw soybean ingestion than the corresponding mean levels determined during the first experimental period. The plasma level of cholecystokinin increased only slightly and in the first days of the second experimental period only. The other gastrointestinal hormones studied were slightly (gastrin) or not (somatostatin, PP) affected by raw soybean feeding. It is suggested that feedback control of exocrine pancreatic secretion in pigs was the mechanism involved in the increase of pancreatic juice observed when raw soybean was fed. This volume increase would result from secretin release into the blood.