Atrial natriuretic peptide reduces inflammation and enhances apoptosis in rat acute pancreatitis.

AIM: We previously reported that atrial natriuretic peptide (ANP) reduces serum amylase and intrapancreatic trypsinogen activation in the onset of acute pancreatitis whereas secretin increases them. In the present work, we sought to establish the effect of ANP and secretin on the inflammatory response and cell death in experimental acute pancreatitis. METHODS: The expression and activity of key inflammatory mediators and apoptosis were evaluated in the presence or absence of the atrial peptide, secretin or both in cerulein-induced acute pancreatitis in rats. Also, ultrastructural changes in pancreatic acinar cells were assessed by transmission electron microscopy. RESULTS: ANP significantly reduced NF-κB activation and TNF-α intrapancreatic levels. Furthermore, it decreased inducible nitric oxide synthase and cyclooxygenase 2 expression and activity while it diminished myeloperoxidase activity. ANP also stimulated apoptosis as shown by caspase-3 expression and activation as well as TUNEL assay. These findings correlated well with the ultrastructural changes observed in the exocrine pancreas. Although secretin reduced various inflammatory markers, it also diminished caspase-3 activation and the overall response was the aggravation of the disease as reflected by the ultrastructural alterations of pancreatic acinar cells. In the presence of ANP, various effects evoked by secretin were antagonized. CONCLUSION: Present findings show that ANP significantly attenuated the severity of acute pancreatitis in the rat by inducing apoptosis and reducing the inflammatory response and further suggest that ANP may have eventual therapeutic implications in the disease and/or in medical interventions at risk of its developing like endoscopic retrograde cholangiopancreatography.

C-type natriuretic peptide applied to the brain enhances exocrine pancreatic secretion through a vagal pathway.

C-type natriuretic peptide (CNP) is the major natriuretic peptide in the brain and its mRNA has been reported in the central nervous system, which supports local synthesis and its role as a neuromodulator. The aim of the present work was to study the effect of centrally applied CNP on pancreatic secretion. Rats were fitted with a lateral cerebroventricular cannula one-week before secretion studies. The central administration of CNP dose-dependently enhanced pancreatic fluid and protein output. CNP response was diminished by atropine and hexamethonium, but it was abolished by vagotomy. Neither adrenergic antagonists nor the administration of (D-p-Cl-Phe(6),Leu(17))-vasoactive intestinal peptide (VIP antagonist) or N(omega) Nitro-L arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) affected CNP response. The effect induced by CNP was mimicked by 8-Br-cGMP but not by c-ANP-(4-23) amide (selective agonist of the natriuretic peptide receptor C). Furthermore, CNP interacted with cholecystokinin (CCK) and secretin in the brain to modify pancreatic secretion. Present findings show that centrally applied CNP enhanced pancreatic secretion through a vagal pathway and suggest that CNP response is mediated by the activation of natriuretic peptide guanylyl cyclase coupled receptors in the brain.

[Gastro-entero-pancreatic hormones in patients with chronic Chagas' disease]. / Hormônios gastro-êntero-pancreáticos em portadores de doença de Chagas crônica.

The seric levels of gastrin, pancreatic glucagon, pancreatic polypeptide, enteroglucagon, motilin and cholecistokinin were evaluated in ten patients with chronic Chagas' disease and compared with those observed in nine normal control subjects. The seric values of all the hormones were determined on basal stimulation, after continuous intravenous secretin infusion and infusion of stepwise increased concentrations of caerulein (direct stimulation), and after intravenous secretin administration followed by intraduodenal instilation of increased concentrations of phenylalanina (combined stimulation). All the hormones, basal and after direct stimulation, showed similar values, except gastrin that in the chagasic group presented higher levels than in control subjects. Phenylalanine and pancreatic polypeptide showed significantly higher values in the control group than in the one of patients with Chagas' disease. The hormonal response in patients with chronic Chagas' disease suggested a neural impairment of the enteropancreatic axis.

Pure pancreatic juice in humans: orange-lemon-juice-induced secretory effects. Comparative analysis with a regular meal, sorbitol, acidified peptone broth and secretin.

The secretory effect elicited by the ingestion of 100 ml of orange-lemon juice (O.-L.J.) was studied on pure pancreatic juice obtained from a catheter placed in the human Wirsung duct at surgery. These changes were compared with those evoked by a regular meal (R.M.), the ingestion of a Sorbitol solution (S.S.), the intragastric infusion of an acidified peptone broth (A.P.B.) and an i.v. single injection of secretin (Boots, 1.0 U/kg). The O.-L.J. induced purer pancreatic secretion response (flow, bicarbonate and enzyme output) than that triggered by the R.M., S.S. and A.P.B. The O.-L.J. evoked peak values, were observed earlier (60 min) than with a R.M. (90 min) ingestion. The 120-min-cumulative values confirmed these findings and disclosed that O.-L.J. elicits a rate of secretion and bicarbonate output closely similar to that of an i.v. secretin injection and amylase response greater than that evoked by this hormone. Thus, O.-L.J. ingestion proved to be an unexpected powerful stimulus of exocrine pancreatic secretion.

Efeito de estímulos fisiológicos sobre a motricidade do esfíncter de Oddi / Effect of physiological stimuli on the Oddi's sphincter motility

A atividade mioelétrica do esfíncter de Oddi foi avaliada tanto nos estados de jejum, como prandial e após a administraçäo de hormônios gastrointestinais que podem desempenhar uma importante funçäo no controle da motricidade do esfíncter de Oddi. A eletromiografia do esfíncter de Oddi e do trato gastrointestinal foi realizada em 21 opossums em jejum e após a administraçäo de 20 Cal/kg de lipídios, proteínas, carboidratos ou de uma mistura isocalórica desses três alimentos. O efeito de hormônios gastrointestinais (colecistoquinina, gastrina, glucagon e secretina) também foi estudado. O segmento proximal do esfíncter de Oddi gerou potenciais de açäo espontâneos que se propagaram para o segmento distal do esfíncter. O esfíncter de Oddi apresenta uma variaçäo na freqüência dos potenciais de açäo durante o jejum que se correlaciona com a atividade mioelétrica do trato gastrointestinal, denominada complexo mioelétrico migratório. Após a administraçäo de alimentos, o complexo mioelétrico migratório foi abolido e substituído por um outro de atividade mioelétrica prandial, cuja duraçäo e freqüência dos potenciais de açäo dependiam do tipo de alimento. A colecistoquinina e a pentagastrina aumentaram e o glucagon e a secretina diminuiram a freqüência dos potenciais de açäo no esfíncter de Oddi. Conclui-se que o esfíncter de Oddi pode desempenhar a funçäo importante de propelir e coordenar o tempo e o volume de drenagem para o duodeno

[Calcium secretion "in vivo" by mouse exocrine pancreas. Relationship with enzymatic output]. / Estudio in vivo de la secreción de calcio por el pancreas exócrino del ratón. Relación con la secreción enzimática.

Calcium secretion and chymotrypsin (CHT) outputs in pancreatic juice from mice were studied "in vivo". Pancreatic juice was collected after stimulation with secretin 32 mU/g. Secretin 32 mU/g plus cholecystokinin 16 mU/g (CCK) or secretin 32 mU/g plus bethanechol 0.2 ug/g. Calcium and CHT outputs were lower in mice treated with secretin alone than in those treated either with secretin plus CCK or with secretin plus bethanechol. Bethanechol or CCK addition to secretin produced a positive correlation between both parameters. Extrapolation of the regression line correlating calcium and CHT outputs indicates that at zero CHT output pancreatic juice contains calcium. These results suggest that calcium in mice pancreatic juice is produced by two different sources.

[Effect of physiological stimuli on Oddi's sphincter motility]. / Efeito de estímulos fisiológicos sobre a motricidade do esfíncter de Oddi.

The myoelectric activity of the sphincter of Oddi was studied both in the fasted and fed states and following administration of gastrointestinal hormones. Electromyographic recordings were obtained from 21 opossums in the fasted state and following administration of 20 Cal/kg of fat, protein, carbohydrate or isocaloric mixture of these three aliments. The proximal segment of the sphincter of Oddi generated spontaneous spike potentials that migrated to the distal segment of the sphincter. The frequency of spike potentials correlated with the migrating myoelectric complex in the duodenum. Following feeding, the migrating myoelectric complex was abolished and substituted by a fed pattern. The duration of the fed pattern and the frequency of spike potentials depended on the kind of aliment. Cholecystokinin and pentagastrin increased and glucagon and secretion decreased the frequency of spike potentials in the sphincter of Oddi. It is concluded from these studies that the sphincter of Oddi may play an important role in controlling the time and rate of biliary drainage into the duodenum.

Estudio in vivo de la secreción de calcio por el páncreas exocrino del raton: relación con la secreción enzimática / In vivo study of the calcium secretion by the exocrine pancreas of mice: relationship with enzymatic secretion

La secreción de calcio y su relación con la secreción de quimiotripsina (QT) por el páncreas del ratón, in vivo, fueron determinadas en jugo pancreático puro colectado bajo tres condiciones de estimulación: secretina 32 mU/gm; secretina 32 mU/mg más colecistocinina 16 mU/gm y secretina 32 mU/gm más betanecol 0.2 ug/gm. En las muestras obtenidas se determinó actividad de quimotripsina y calcio secretado en 30 minutos luego de la estimulación. La secreción de calcio y QT fue mayor en ratones tratados con secretina más CCK y secretina más betanecol. En estos dos últimos grupos, entre ambos parámetros se estableció una correlación positiva. Las rectas obtenidas no fueron diferentes de una recta única y la extrapolación al origen indica que existe calcio en el jugo pancreático aún ausencia de secreción enzimática. Los resultados obtenidos concuerdan con la existencia de al menos dos mecanismos diferentes de secreción de calcio por el páncreas exocrino del ratón

Estudio in vivo de la secreción de calcio por el páncreas exocrino del raton: relación con la secreción enzimática / In vivo study of the calcium secretion by the exocrine pancreas of mice: relationship with enzymatic secretion

La secreción de calcio y su relación con la secreción de quimiotripsina (QT) por el páncreas del ratón, in vivo, fueron determinadas en jugo pancreático puro colectado bajo tres condiciones de estimulación: secretina 32 mU/gm; secretina 32 mU/mg más colecistocinina 16 mU/gm y secretina 32 mU/gm más betanecol 0.2 ug/gm. En las muestras obtenidas se determinó actividad de quimotripsina y calcio secretado en 30 minutos luego de la estimulación. La secreción de calcio y QT fue mayor en ratones tratados con secretina más CCK y secretina más betanecol. En estos dos últimos grupos, entre ambos parámetros se estableció una correlación positiva. Las rectas obtenidas no fueron diferentes de una recta única y la extrapolación al origen indica que existe calcio en el jugo pancreático aún ausencia de secreción enzimática. Los resultados obtenidos concuerdan con la existencia de al menos dos mecanismos diferentes de secreción de calcio por el páncreas exocrino del ratón (AU)

[Secretin and pancreatic secretion in iron absorption]. / Secretina y secreción pancreática en la absorción de hierro.

Iron absorption in dogs without pancreatic secretion was studied measuring the percentage of radioactivity retained in red cells. Two groups were treated con 59Fe (5 microCi), given in the stomach: one group control and other undergoing pancreatic duct ligation. Increased absorption was observed in the last group. The influence of secretion on iron absorption, after administration of 60 mg of Fe (as ferrous sulphate solution pH 4.5), was also studied in three groups of dogs, treated with 18 Clinical Units of secretin. In one group, the pancreatic secretion was extracted from intestine by putting a catheter in the pancreatic duct. In the other two, the pancreatic duct remained normal, one with and other without the iron dose (control). A possible inhibitory effect of secretin on iron absorption was observed. Plasma Iron values remained without changes one hour after the iron administration, as well as TIBC, % saturation and transferrin values.

Secretina y secrecion pancreatica en la absorcion de hierro / Secretin and pancreatic secretion in the iron absorption

Se estudió en perros la absoción del hierro, en ausencia de secreción pancreática, midiendo el porcentaje de radioactividad retenada en glóbulos rojos después de la administración de 59 Fe. Se obtuvo un aumento de absorción. También se estudió la influencia de la secretina sobre la absorción, por la variación de la sideremia después de una dosis de sulfato ferroso (60 mg) como FeSO4 7H20, pH4.5. Se trabajó con 5 lotes de perros. A dos de los grupos se administró 59 Fe (% uCi) en el estómago: uno control y otro con conducto pancreático ligado, obteniéndose los siguientes % de absorción: 8,54 + ou - 0.72 y 10.37 + ou - 1,02% respectivamente. Los otros tres grupos fueron tratados con secretina (18 Unidades Clínicas): el 1o con operación simulada, el 2o con conducto pancreático canalizado al exterior y el 3o control de los niveles de sideremia. Se observa una posible acción inhibidora de la secretina. La sideremia no varió a la hora después de administrada la dosis de hierro. Tampoco se observa modificación en los valores de TIBC, saturatión % y siderofilina (AU)

Secretina y secrecion pancreatica en la absorcion de hierro / Secretin and pancreatic secretion in the iron absorption

Se estudió en perros la absoción del hierro, en ausencia de secreción pancreática, midiendo el porcentaje de radioactividad retenada en glóbulos rojos después de la administración de 59 Fe. Se obtuvo un aumento de absorción. También se estudió la influencia de la secretina sobre la absorción, por la variación de la sideremia después de una dosis de sulfato ferroso (60 mg) como FeSO4 7H20, pH4.5. Se trabajó con 5 lotes de perros. A dos de los grupos se administró 59 Fe (% uCi) en el estómago: uno control y otro con conducto pancreático ligado, obteniéndose los siguientes % de absorción: 8,54 + ou - 0.72 y 10.37 + ou - 1,02% respectivamente. Los otros tres grupos fueron tratados con secretina (18 Unidades Clínicas): el 1o con operación simulada, el 2o con conducto pancreático canalizado al exterior y el 3o control de los niveles de sideremia. Se observa una posible acción inhibidora de la secretina. La sideremia no varió a la hora después de administrada la dosis de hierro. Tampoco se observa modificación en los valores de TIBC, saturatión % y siderofilina

Stimulation by gastro-intestinal hormones of cyclic adenosine 3': 5'-monophosphate accumulation and insulin release in isolated pancreatic islets of the rat.

In collagenase isolated rat pancreatic islets, CCK-PZ, SHG, secretin and glucagon stimulated the accumulation of cAMP, in physiological ranges. The resulting increment of cAMP showed a good correlation with insulin release stimulated by either glucagon or secretin, but not by SHG or CCK-PZ. In the same system, 14CO2 production from glucose-U-14C was significantly increased by either SHG or CCK-PZ. The results presented in this report are compatible with the hypothesis that insulin release by gastrointestinal hormones may be mediated by cAMP in the B-cell in the case of either glucagon or secretin; whereas, in the case of either SHG or CCK-PZ, it may presumably be mediated by an unknown mechanism in glucose metabolism, other than c-AMP.