Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95 percent CI: 4.1-152 nM) and cerulein (EC50: 58; 95 percent CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95 percent CI: 2.5-18 æM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 æM L-NOARG from 73 ± 5.1 to 19 ± 3.5 percent in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

Secretory response of cultured acinar cells of rat pancreas to cholecystokinin

To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acina response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.

O esôfago na doença de chagas: estudos fisiológicos, farmacológicos e clínicos / The esophagus in chagas's disease: physiological, pharmacological and clinical studies

A desnervaçäo intramural, comprovada anatomopatologicamente e por meio de teste farmacológico, é a responsável fundamental pela acalásia da cardia e pela ausência de peristaltismo no corpo do esôfago na moléstia de Chagas. A dificuldade de trânsito e a estase resultantes determinam os principais sintomas e complicaçöes do megaesôfago. Dentre as recentes aquisiçöes na fisiopatologia e farmacologia do megaesôfago, obtidas pelo método manométrico, pode-se destacar: o retarde no tempo faringo-esofágico, a concomitância de peristaltismo e aperistalse, e respostas anormais do esfíncter inferior à ceruleina, à atropina, à nifedipina e ao dinitrato de isosorbitol. Mostrou-se que a gamacintilografia é útil no estudo do trânsito esofagiano no megaesôfago pois pode propiciar a detecçäo de anormalidades insuspeitadas, sobretudo quando a deglutiçäo é feita com o paciente deitado, bem como, permitir uma visäo dinâmica e quantitativa das alteraçöes do esvaziamento esofágico

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

Effects of Pancreatic Polypeptide on the Secretion of Enzymes and Electrolytes by in Vitro Preparations of Rat and Cat Pancreas

Pancreatic polypeptie (PP) is released from the pancreas in response to vagal stimulation. Amongst other effects, PP has been reported to inhibit pancreatic exocrine function. Apart from any potential physiological role, such inhibition could have important consequences for in vitro studies of pancreatic function employing acetylcholine as a stimulus. We have therefore tested the effect of bovine PP on two in vitro pancreatic preparations: the incubated, uncinate pancreas of young rats and the perfused cat pancreas. In the former, PP (10(-10)-10(-8)M) had little or no effect on enzyme discharge or45Ca efflux under basal conditions or during stimulation with caerulein, CCK-PZ or acetylcholine. In the perfused cat pancreas, similar concentrations of PP were also without effect on fluid secretion evoked by secretin infusion, or enzyme discharge evoked by CCK-PZ injection or infusion. We conclude that bovine PP has no direct effects on the cellular mechanisms responsible for pancreatic electrolyte secretion or enzyme discharge in the species studied.