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Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

The responses of pancreas acini from Hooded-Lister rats to kidney bean E 2 L 2 lectin or soybean agglutinin have been studied in vitro . Both lectins induced secretion of α-amylase from acini in a dose dependent manner. However, the concentrations of lectin required to cause enzyme secretion were approximately 14-fold higher than that necessary with CCK-8. In addition, the responsiveness of pancreas acini to lectins in vitro was significantly altered by the age and sex of the rats from which the acini were derived.

The use of acid suppression in patients with exocrine pancreatic insufficiency (EPI) additionally to enteric-coated pancreatic enzyme preparations (PEPs) is controversial. In current recommendations, the prescription of proton pump inhibitors (PPIs) is not generally recommended, but mentioned as an auxiliary agent if PEPs alone are not effective and a dose augmentation does not lead to a satisfying improvement of symptoms. Adverse effects of PPI treatment are rare while several beneficial aspects of their use in patients with EPI have become evident. The addition of PPIs to PEPs in patients with EPI results in a higher duodenal pH and thus a reduced inactivation of the residual enzyme secretion of patients, an earlier dissolution of PEPs from enteric coating, and a prevention of bile salt precipitation. These factors contribute to a more effective and physiological digestive pattern in patients with EPI. This article gives a detailed overview of why we believe the recommendation for the use of acid-suppressing drugs in patients with EPI is justified.

Captopril enhanced exocytotic enzyme secretion from rabbit peritoneal neutrophils activated by suboptimal concentrations of fMet-Leu-Phe. For optimal enhancement the presence of Ca2+ was required. Captopril did not induce enzyme secretion by its own, and there was little effect on PMA-induced exocytosis. Cyclic GMP level of neutrophils was transiently enhanced by captopril. Methylene blue inhibited both captopril-induced enhancement of enzyme release and of cGMP levels. From our studies and from reports in the literature it appears that cGMP level-enhancing compounds may have both activating or inhibitory properties.

Pancreatic acini from most species possess vasoactive intestinal peptide (VIP) receptors. Recently, two subtypes of VIP receptors, VIP1-R and VIP2-R, were cloned. Which subtype exists on pancreatic acini or mediates secretion is unclear. To address this, we examined pancreatic acini from both rat and guinea pig. VIP1-R and VIP2-R mRNA were identified in dispersed acini from both species by Northern blot analysis and in rat by Southern blot analysis. With the use of the VIP2-R-selective ligand Ro-25-1553 in both species, inhibition of binding of125I-labeled VIP to acini showed a biphasic pattern with a high-affinity component (10%) and a second representing 90%. The VIP1-R-selective ligand, [Lys15,Arg16,Leu27]VIP-(1—7)-GRF-(8—27), gave a monophasic pattern. Binding of Ro-25-1553 was better fit by a two-site model. In both rat and guinea pig acini, the dose-response curve of Ro-25-1553 for stimulation of enzyme secretion was biphasic, with a high-affinity component of 10–15% of the maximal secretion and a low-affinity component accounting for 85–90%. At low concentrations (10 nM) of Ro-25-1553 and [Lys15,Arg16,Leu27]VIP-(1—7)-GRF(8—27), which only occupy VIP receptors, a 4-fold and a 56-fold increase in cAMP occurred, respectively. These results show that both VIP1-R and VIP2-R subtypes exist on pancreatic acini of rat and guinea pig, their activation stimulates enzyme secretion by a cAMP-mediated mechanism, and the effects of VIP are mediated 90% by activation of VIP1-R and 10% by VIP2-R. Because VIP has a high affinity for both VIP-R subtypes, its effect on pancreatic acini is mediated by two receptor subtypes, which will need to be considered in future studies of the action of VIP in the pancreas.

During a secretin-cerulein test for exocrine pancreatic function, venous acid-base analysis was performed before and 30 and 45 min after the intravenous injection of secretin (1 clinical unit/kg body weight). A decrease in plasma bicarbonate was observed in persons with normal exocrine pancreatic function as defined by normal bicarbonate and enzyme secretion in the secretin-cerulein test (n = 39). Bicarbonate values were 94.8 +/- 3.6% (mean +/- SD) of the initial concentration after 30 min and 92.9 +/- 3.9% after 45 min. In contrast, there was no statistically significant decrease in plasma bicarbonate in patients with global pancreatic exocrine deficiency (n = 15). In normal exocrine pancreatic function, the maximal plasma bicarbonate decrease was 2.17 +/- 1.12 mM (mean +/- SD; n = 39). In patients with global exocrine deficiency, however, a maximal plasma bicarbonate decrease of 0.54 +/- 0.68 mM (n = 15) was obtained. The difference was highly significant (p0.001). In patients with partial exocrine deficiency (isolated decrease in bicarbonate secretion or reduced excretion of a single enzyme), values were also significantly lower (1.44 +/- 1.40 mM; n = 14; p0.05). The maximal plasma bicarbonate decrease correlated with the bicarbonate secretion into the duodenal juice (r = 0.62, p0.001). If a maximal plasma bicarbonate decreaseor = 0.9 mM was considered normal, determination of plasma bicarbonate following secretin administration allowed us to detect the presence of global exocrine deficiency with a sensitivity of 87% and a specificity of 87%. The secretin-induced plasma bicarbonate decrease may therefore be used as a new simple tubeless test to evaluate exocrine pancreatic function.

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment. In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.

The pathophysiology of acute pancreatitis remains controversial. Activation of digestive enzymes in the pancreas may play an important role in the course of this disease. Therefore, the inhibition of enzyme secretion may be a possible treatment concept. However, it is not clear whether pancreatic secretion continues during the course of acute pancreatitis. In the present paper experimental and clinical studies are reviewed to evaluate the effect of somatostatin and octreotide treatment in acute pancreatitis.

Publisher Summary An advance in the study of pancreatic function in vitro was the development of a technique for preparing dispersed pancreatic acinar cells. This preparation consisted of a homogeneous suspension of dispersed single acinar cells. Freshly prepared dispersed acini can be used for at least 5 hr in vitro and have been very useful to investigate the mechanism of action of various secretagogues. Dispersed acini have been prepared using pancreas from mice, rats, guinea pigs, or rabbits. The procedure for preparing dispersed pancreatic acini in culture is an aseptic modification of the techniques reported previously for preparing fresh dispersed pancreatic acini. This method allows one to study long term actions of various agents. During the last decade dispersed pancreatic acini have been used much more extensively than acinar cells, primarily because acini are easier to prepare and show a much greater increase in enzyme secretion in response to secretagogues than do acinar cells.

The effect of feeding an alpha-amylase inhibitor (BAY e 4609, 700 mg/100 g food) for 20 or 90 days on the enzymes of the exocrine pancreas of the rat was investigated. The amylase inhibitor-fed rats gained significantly less weight despite a higher food intake than control rats on a standard diet. Fecal weight increased threefold. Pancreatic wet weight, pancreatic DNA, protein and insulin concentrations were not influenced. The amylase content of the pancreas was significantly diminished compared with controls. The trypsin level increased and the changes in the amount of lipase were not significant. Also in response to an infusion of 15 or 60 IU CCK/kg/h combined with 0.5 clinical units of secretin/kg/h amylase secretion was significantly diminished after both feeding periods compared with controls, while trypsin output increased as did the output of lipase to a lesser extent. The enzyme pattern of the pancreatic juice reverted to normal when the animals consumed the control diet again. Gut weight and length increased significantly in the experimental animals. It is concluded that the changes in the pancreatic enzymes are induced by altered food intake. The amylase inhibitor prevents the digestion of starch and by this carbohydrate absorption. As a consequence, hyperphagia develops resulting in an increased protein and fat intake. Unlike trypsin a negative feedback regulation does not exist between alpha-amylase concentration in the gut and pancreatic enzyme secretion.

The secretory response of the exocrine pancreas to an intravenous bolus of secretin (1.0 U/kg) was studied in healthy men and women below and above 45 years of age. We studied the secretory pattern, i.e., electrolyte and enzyme secretion in 8 sequential, 10-min collections and cumulative values for each parameter. Within the male group, no significant changes were observed, except for higher amylase and lipase secretions in the older subjects. On the other hand, females over 45 yr old had secretory patterns that showed a decline of flow and of bicarbonate concentration and output. No significant secretory differences were observed in the groups of younger males and females. When the over-45 groups of men and women were compared, the women exhibited a significant decrease in bicarbonate concentration and output. Moreover, this group of women had a cumulative 80-min output of bicarbonate and lipase significantly below these parameters in the men. Possible mechanisms are discussed.

The effects of a new H2-receptor blocker, ranitidine, given intravenously (for comparison with cimetidine) or orally an gastric and pancreatic secretion have been studied in duodenal ulcer patients. Ranitidine appears to be several times more potent and a longer-acting inhibitor of gastric secretion than cimetidine. This H2 blocker does not affect pancreatic bicarbonate and enzyme secretion.

Isoproterenol was shown to stimulate amylase secretion from the isolated perfused cat pancreas. Results suggest that isoproterenol acts on pancreatic β-receptors and that endogenously released acetylcholine is responsible for enzyme secretion.

The effect of intraduodenally administered cattle bile, Na-taurodeoxycholate, and Na-taurocholate on secretin-stimulated exocrine pancreatic secretion was investigated on 40 fasting young healthy volunteers. Intraduodenal bile stimulated significantly and dose-dependently hydrokinetic and ecbolic pancreatic secretion. Only bile, but not secretin intravenously, both applied in a dosage equivalent with respect to their hydrokinetic action, caused a significant increase of enzyme output and enzyme concentration as well. Intraduodenal Na-taurodeoxycholate enhanced also dose-dependently secretin-stimulated volume, bicarbonate, and enzyme secretion. The effect was related to the load, not to the concentration of this bile salt. On the other side, Na-taurocholate had only a weak and not dose-dependent hydrokinetic and no ecbolic effect. It is concluded that not bile salts in general, but only certain of them--like Na-taurodeoxycholate--are the effective constituents of bile, acting as specific intraduodenal stimulants of hydrokinetic and ecbolic pancreatic secretion.

1. 1. The responsiveness of adenylate cyclase and enzyme secretion for secretin and the C-terminal octapeptide of pancreozymin has been investigated in particulate fractions of the pancreas of five different species. 2. 2. The adenylate cyclase is sensitive to the C-terminal octapeptide of pancreozymin in all species investigated. 3. 3. The enzyme is much more sensitive to secretin in rat and cat than in mouse and rabbit, whereas with guinea pig intermediate values are obtained. 4. 4. The enzyme secretion is stimulated by secretin in pancreatic fragments of rat and cat, but not in those of mouse and rabbit. 5. 5. These results suggest that in species where secretin stimulated enzyme secretion, it does so by stimulating the adenylate cyclase system.

We have studied the effects of cholecystokinin-pancreozymin (CCK-PZ) from the GIH laboratory in Stockholm, Sweden, on the electrolyte and enzyme secretion of the pancreas. CCK-PZ in variable doses has been given together with a constant secretin dose of 2 clinical units per kilogram hour (CU/kg-hr). The results obtained were compared with a second group of tests where secretin alone was administered in the same dose. CCK-PZ given with the same dose of secretin that produced maximal fluid and electrolyte flow does not potentiate the total bicarbonate response but does slightly increase bicarbonate concentration. The variations observed are due to the presence of acinar and biliary factors. On the other hand, administration of CCK-PZ produces a greater maximal enzyme response than we have obtained in prior studies after injection of Boots pancreozymin or caerulein. For this reason we prefer CCK-PZ to other products in pancreatic studies.

The effects of porcine cholecystokinin (CCK) and secretin on gastric enzyme secretion in Styela clava were measured using a perfusion technique. Secretin was found not to be active, whereas CCK and CCK-octapeptide were both found to stimulate gastric release of acid phosphatase and proteins. Varying doses of CCK, between 0.1 and 1.0 mg, produced an approximately linear dose/response. It is suggested that these results are evidence of a paracrine system involving a prosecgastrin-like molecule, produced in the gastric epithelium.

Summary Pancreatic dose-response relationship to graded doses of caerulein, infused intravenously over a continuous secretin background, was studied in rats under acute fistula conditions. In comparison with rats which did not receive secretin, the flow of juice was significantly increased in response to doses of the peptide from 33.75 to 101.25 ng kg −1 min −1 , but only the rate of 101.25 ng kg −1 min −1 produced a significant increase of amylase output. A good correlation between flow and enzyme secretion was shown. Amylase concentrations were about 30% lower than in animals not infused with secretin. The secretin background determined an increase of the calculated maximal response of amylase secretion to caerulein and a decrease of the value of ED 50 of the peptide.

This article presents results of examination of the compensatory processes and the function of the digestive system after partial (two-thirds and four-fifths) resection of the stomach in dogs. These data were obtained in experiments on 28 dogs, observed up to 2 years after the operation. The secretory function and the enzyme secretion of the stomach, pancreas and small intestine, as well as the motor function and absorptive property of the small intestine, were studied.

dl-ethionine fed orally to rats for 15, 20, and 25 days produced pancreatic acinar atrophy to the degree that when acute bile-salt pancreatitis was induced, lytic phenomena—fat and alveolar necrosis—were inhibited, although the inflammatory reaction was histologically uninfluenced. It is thought that this inhibition is the result of a markedly decreased enzyme secretion.

The effects of various concentrations of epinephrine and dibutyryl cyclic 3′, 5′-AMP (dcAMP) on enzyme secretion and glucose oxidation by rat parotid in vitro were determined. Epinephrine at 0.33 μg/ml increased α-amylase secretion 43% without significantly altering glucose oxidation. Higher concentrations of epinephrine increased both secretion and glucose oxidation. The cyclic 3′,5′ -AMP (cAMP) derivative dcAMP stimulated amylase secretion 157% at 200 μg/ml without producing any accompanying increase in glucose oxidation. These results indicate that changes in oxidation are not essential for the cAMP induced phase of enzyme secretion and that the increase in glucose oxidation produced by epinephrine is not mediated by cAMP.

A study was made of the secretory and enzyme-secretory function of the small intestine in dogs following resection of its superior and inferior portions. Periodic secretion and the secretion occurring after the irrigation with a 10% peptone solution were studied.

Isolierte Submandibularisdrusen des Meerschweinchens wurden in physiologischer Pufferlosung mit sekretionsstimulierenden Substanzen inkubiert. Dopamin, Noradrenalin, Adrenalin und 5-HT induzieren die Sekretion von Peroxydase und Amylase, wahrend der Serotoninantagonist BOL 148 (2-Bromo-d-Lysergsaure Dietylamid) eine beinahe vollstandige Sekretionshemmung hervorruft. BOL 148 hat sich also nicht als spezifisch 5-HT-hemmend an der Meerschweinchenspeicheldruse erwiesen.

Lysosomal enzyme secretion by skin fibroblasts derived from cystic fibrosis homozygotes and normal donors of the same range of age, sex and culture passage number were compared. No differences were detected between these groups in their rates of spontaneous lysosomal enzyme release. Incubation of either normal or cystic fibrosis fibroblasts with cystic fibrosis serum did not alter these secretion rates. The lysosomal enzyme secretion of both normal and cystic fibrosis fibroblasts responded similarly to incubation with NH4Cl, monensin, A23187, trifluoperazine or Cytochalasin B. It was concluded that lysosomal enzyme hypersecretion, which has previously been suggested to occur in cystic fibrosis, is unlikely to provide a reliable diagnostic test for the disease.

Pancreatic lipase and trypsin have been measured autotitrigraphically in duodenal aspirate both before and for 3 hours after an oral test feed. These studies concern 12 normal newborns, gestational maturity 34±2 weeks (M±SD), at approximately 2 weeks of age, and 14 apparently normal children aged 3–72 months. A consistent pattern of enzyme activity was found, with higher activity in the resting samples and in the third hour compared to very low activity during the first post-prandial hour. There was a significantly higher mean lipase activity in children compared with that in newborns (P=0.001) which was not so for mean trypsin. An estimate oftotal enzyme secretion by the pancreas was devised using determinations of polyethylene glycol in test feed and duodenal contents; this also allowed intergroup comparison since there was a significant difference between the groups in the degree to which test feed diluted enzyme activity (P

Biochemical studies of pancreatic juice collected by duodenal aspiration and endoscopic cannulation of the main pancreatic duct were performed and compared in the same fasted normal subjects in seven cases. The comparison of the results shows that under the same stimulation (0.5 CU/kg/hr of GIH secretin and 75 ng/kg/hr of cerulein) the endoscopic cannulation of the main pancreatic duct provides the best values for the maximal secretory capacity. On the other hand, this technique is no better than our current method of duodenal aspiration for the exploration of the enzyme secretion.

Summary: Five different enzyme activities were estimated in ejaculates obtained from 96 men visiting our infertility clinic. Sperm count showed a significant positive correlation with aspartate-aminotransferase (GOT) and alanine-aminotransferase (GPT). Acid phosphatase was positively correlated with gamma-glutamyl transpeptidase (GGTP) and citrate and negatively with fructose. GGTP showed similar relationships with citrate and fructose. For beta-glucuronidase a low positive correlation with GGTP and GOT was detected. The enzyme activities of 27 ejaculates with a high viscosity were not significantly different from the activities of ejaculates with normal liquefaction. The conclusion is reached that insufficient prostatic enzyme secretion is not the cause of abnormal liquefaction in these patients. Enzym-Aktivitat im menschlichen Ejakulat: Beziehungen zur gestorten Verflussigung Zusammenfassung: In den Ejakulaten von 96 Mannern wurden funf verschiedene Enzym-Aktivitaten untersucht. Die Spermatozoendichte zeigte eine positive Korrelation mit GOT und GPT. Die saure Phosphatase war positiv korreliert mit GGTP und Zitrat, dagegen negativ mit Fruktose. GGTP zeigte ahnliche Relationen mit Zitrat und Fruktose. Fur beta-Glukuronidase konnte eine geringe positive Korrelation mit GGTP und GOT bestimmt werden. Die Enzymaktivitaten von 27 Ejakulaten mit einer hohen Viskositat waren nicht signifikant unterschieden von den Aktivitaten der Ejakulate mit einer normalen Verflussigung. Es ergibt sich nach Auffassung der Autoren die Schlusfolgerung, das eine insuffiziente Prostata-Enzym-Sekretion keinen ursachlichen Faktor fur die abnormale Verflussigung der Ejakulate dieser Patienten darstellt.

The exocrine pancreas serves an important function in digestion and absorption of nutrients by secreting digestive enzymes into the lumen of the small intestine.

In un sistema di fette di pancreas di cavia incubate in vitro l'adrenalina non modifica l'attivita secretoria delle cellule acinari ne in condizioni basali ne in risposta a farmaci segretagoghi (ceruleina e carbamoilcolina). Sembra quindi probabile che l'inibizione della secrezione pancreatica esocrina prodotta in vivo dalla iniezione di adrenalina sia dovuta ad un meccanismo indiretto, quale la vasocostrizione pancreatica e(o) l'inibizione della secrezione di acqua ed elettroliti a livello delle cellule acino-duttulari.

In cystic fibrosis, the turbid submandibular saliva contains excess calcium, protein and amylase. The calcium is partially precipitated as hydroxyapatite and it is concentrated and secreted in rat parotid zymogen granules. This study has confirmed elevated calcium, protein and amylase in cystic fibrcsis submandibular saliva, and has shown the amylase to be in solution. The turbid, insoluble fraction was composed predominantly of subcellular particles, which have been identified by electrcn microscopy as inclusion bodies from submandibular zymogen granules It was postulated that in cystic fibrosis, hypersecretion of zymogen granules causes the elevated submandibular saliva calcium, and that the resultant precipitated hydroxyapatite prevents dissolution of the granular inclusion bodies. This insoluble material was proposed as the cause of duct obstruction in the submandibular gland.

The functions of the pancreas will never be understood until there are methods for ascertaining its fundamental physiology. On this question a great deal of work is now being done. Of course, the function of the pancreas that is most obvious is the enzyme secretion. How to estimate it in some manner accurate enough for clinical investigation is the problem discussed in this article. There has been a great deal of study of the pure secretion, but that is of only academic help in the clinical problems. A method of approach which will give a fairly faithful record of the functional state of the pancreas in its production of the so-called external enzymes is offered here. To begin with, an estimation was made of the amount of starch digested as shown in various dilutions of duodenal contents with the aid of iodine. Among the first to do this was Dr.