Effects Of Gastrointestinal Hormones Research Articles

The effects of glucagon like peptide-1 (GLP-1) on cardiac remodeling: exploring the role of medication and physiological modulation after metabolic surgery.

Obesity and associated comorbidities reach epidemic proportions nowadays. Several treatment strategies exist, but bariatric surgery has the only longstanding effects. Since a few years, there is increasing interest in the effects of gastro-intestinal hormones, in particular Glucagon-Like Peptide-1 (GLP-1) on the remission of Type 2 Diabetes (T2DM) and its effects on cardiac cardiovascular morbidity, cardiac remodeling, and mortality. In the past years several high quality multicenter randomized controlled trials were developed to assess the effects of GLP-1 receptor agonist therapy on cardiovascular morbidity and mortality. Most of the trials were designed and powered as non-inferiority trials to demonstrate cardiovascular safety. Most of these trials show a reduction in cardiovascular morbidity in patients with T2DM. Some follow-up studies indicate potential beneficial effects of GLP-1 receptor agonists on cardiovascular function in patients with heart failure, however the results are contradictory, and we need long-term studies to make firm conclusions about the pleiotropic properties of incretin-based therapies. However, it seems that GLP-1 receptor agonists have different effects than the increased GLP-1 production after bariatric surgery on cardiovascular remodeling. One of the hypotheses is that the blood concentrations of GLP-1 receptor agonists are three times higher compared to GLP-1 increase after bariatric and metabolic surgery. The purpose of this narrative review is to summarize the effects of GLP-1 on cardiovascular morbidity, mortality and remodeling due to medication but also due to bariatric and metabolic surgery. The second objective is to explain the possible differences in effects of GLP-1 agonists and bariatric and metabolic surgery.

Changes in eating behavior, taste and food preferences and the effects of gastrointestinal hormones

Summary Eating behavior is a complex response to different internal and external factors and whose aim is to preserve the homeostasis of energy intake, the stability of body weight and ultimately health. Although under physiological conditions, energy intake is relatively stable over the long period, many stimuli (i.e., mechanical, metabolic, environmental, etc.) may acutely influence energy intake. To offset or minimize the effects of such stimuli on energy homeostasis, humans are equipped with neuronal complex mechanisms integrating peripheral and environmental signals. In particular, eating behavior is determined by homeostatic feeding and hedonic feeding. In the presence of changes in taste or smell, these mechanisms interact with peripheral effectors, including gastrointestinal peptides, to preserve energy intake and ultimately body weight. Aging is associated with a progressive inability of these systems to protect net food intake. Also, changes of eating behavior during disease appear to be related to the activation of a specific neuronal emergency circuit, which promotes anorexia. The persistence during evolution of the emergency pathway suggests that still unidentified component of anorexia and fasting metabolism could be exploited to enhance recovery of patients with acute and possibly chronic diseases.

Attenuated regional vasodilatory effects of gastrointestinal hormones in obesity prone animals: implications for obesity‐related hypertension

Obese animals have reduced renal and splanchnic sympathoinhibitory responses to gastrointestinal hormones that may have implications for increased vascular resistance. Our aim was to determine whether the vasodilatory effects induced by gastric leptin and cholecystokinin (CCK) are also attenuated in obesity. Male Sprague‐Dawley rats were fed a medium high fat diet (MHFD; n=24) or a low fat diet (LFD; n=8) for 13 weeks. Based on weight gain, MHFD rats were stratified into obesity prone (OP; upper tertile; n=8) or obesity resistant (OR; lower tertile; n=8) groups. Baseline arterial pressure (AP) was recorded in isoflurane‐anesthetised rats and Doppler flow probes were attached to the renal and superior mesenteric (SM) arteries for measurement of vascular conductance (VC). CCK was administered intravenously (0.1‐4 μg/kg) and leptin (15 μg/kg) infused close to the coeliac artery. OP rats had elevated AP compared to both LFD and OR rats (P<0.05 for all). CCK increased renal VC in LFD and OR rats and this response was blunted in OP rats (0.5‐4 μg/kg; P<0.05 for all). Leptin significantly increased renal VC in LFD compared to OP rats (P<0.05). In the SM artery, CCK increased VC in LFD animals, and this response was attenuated in OP rats (1–2 μg/kg; P<0.05 for all). Reduced vasodilatory effects of gut hormones may contribute to elevated vascular resistance associated with obesity‐related hypertension.

Incretin physiology beyond glucagon‐like peptide 1 and glucose‐dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides

Gastrin and cholecystokinin (CCK) are homologous hormone systems known to regulate gastric acid secretion, gallbladder emptying, and cell growth in the pancreas and stomach. They are, however, also involved in the development and secretory functions of pancreatic islet cells. For instance, foetal and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man. Accordingly, endogenous hypergastrinaemia is accompanied by islet cell hyperplasia and increased insulin secretion. Conventionally, the effect of gastrointestinal hormones on insulin secretion (the incretin effect) has been defined and quantified in relation to oral versus intravenous glucose loadings. Under these unphysiological conditions, the release of gastrin and CCK and, hence, their effect on insulin secretion are modest in comparison with the effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1). Consequently, the interest of CCK and gastrin in incretin research has for decades been limited. A few years ago, however, it was suggested that gastrin together with epidermal growth factor or later GLP-1 might stimulate beta cell growth and secretion. Recent studies have shown that the combination of gastrin and GLP-1 actually restores normoglycaemia in diabetic mice. Therefore, a short review of the incretin system in a broader functional context that includes gastrin and CCK peptides may be timely.

Effect of gastrointestinal hormones on blood flow through the superior mesenteric artery in the pig.

Summary The effect of close intra-arterial infusion of porcine cholecystokinin, its C-terminal octapeptide, porcine secretin, porcine VIP, bovine glucagon, and pentagastrin on blood flow through the superior mesenteric artery was studied in 30 anesthetized pigs. Carotid artery pressure was also measured. The gastrointestinal hormones induced a more or less pronounced increase in mesenteric blood flow. The effects of cholecystokinins and VIP were more pronounced than those of the other hormones. Infusion of cholecystokinins, pentagastrin, and secretin induced no change or a small decrease in carotid artery pressure whereas VIP and glucagon infusion resulted in a pronounced hypotension. Atropine completely or significantly inhibited the effects of cholecystokinin but had no effect on the VIP-induced vascular changes. Zusammenfassung Einflus gastrointestinaler Hormone auf die Blutstromung in der Arteria mesenterica cranialis des Schweines Bei 30 narkotisierten Schweinen wurde die Wirkung folgender gastrointestinaler Hormone (intraarterielle Infusion) auf die Blutstromstarke in der A. mesenterica cranialis untersucht: Schweine-Cholecystokinin (CCK), C-terminales Octapeptid von CCK, Schweine-Sekretin, vasoaktives Intestinal-Peptid (VIP) des Schweines, bovines Glukagon und Pentagastrin. Auch der Druck in der A. carotis wurde gemessen. Die gastrointestinalen Hormone induzierten eine mehr oder weniger ausgepragte Erhohung der Blutstromung in der Mesenterialarterie. Die Effekte der Cholecystokinine und des VIP waren starker als diejenigen der anderen Hormone. Die Infusion von Cholecystokininen, Pentagastrin und Sekretin hatte keinen Effekt bzw. nur eine geringe Abnahme des Druckes in der A. carotis zur Folge. VIP und Glukagon senkten hingegen den Blutdruck. Atropin hemmte den CCK-Effekt vollstandig oder wenigstens signifikant, jedoch nicht den VIP-Effekt. Resume Influence d'hormones gastro-intestinales sur le debit sanguin dans l'artere mesenterique crâniate du porc On a recherche l'action des hormones gastro-intestinales suivantes chez 30 porcs en narcose (infusion intraarterielle) sur la valeur du debit sanguin dans A. mesenterica cranialis: cholecystokinine (CCK) du porc, octapeptide C-terminal de CCK, secretine du porc, peptide intestinal vasoactif du porc (VIP), glucagon bovin et pentagastrine. La pression dans A. carotis fut egalement mesuree. Les hormones gastrointestinales ont provoque une augmentation plus ou moins marquee du debit sanguin dans l'artere mesenterique. Les effets de la cholecystokinine et de VIP furent plus forts que ceux des autres hormones. L'infusion de cholecystokinine, de pentagastrine et de secretine n'a eu aucun effet si ce n'est une faible diminution de la pression dans A. carotis. VIP et glucagon ont par contre abaisse la pression sanguine. L'atropine a bloque l'effet de CCK completement ou du moins de facon significative, ce qui n'a pas ete le cas pour l'effet de VIP. Resumen Influjo de las hormonas gastrointestinales sobre la circulacion sanguinea en la arteria mesenterica craneal del cerdo En 30 cerdos narcotizados se estudio la accion de las hormonas gastrointestinales (infusion intraarterial) siguientes sobre el caudal sanguineo en la arteria mesenterica craneal: colecistoquinina porcina (CCQ), octapeptido terminal en C de la CCQ, secretina porcina, peptido intestinal vasoactivo (PIV) del cerdo, glucagon bovino y pentagastrina. Tambien se midio la presion en la arteria carotida. Las hormonas gastrointestinales inducian un aumento mas o menos pronunciado del torrente sanguineo en la arteria mesenterica. Los efectos de la CCQ y del PIV eran mas acusados que los de las hormonas restantes. La infusion de las colecistoquininas, pentagastrina y secretina no inducian cambio alguno resp. solo una disminucion ligera de la presion en la carotida. Sin embargo, el glucagon y el PIV ocasionaban una hipotension pronunciada. La atropina inhibia el efecto de la CCQ por completo o al menos significantemente, pero no mostraba efecto alguno sobre los cambios vasculares inducidos por el PIV.

Treatment of Postoperative Enterocutaneous Fistulas with Octreotide in Two Neonates

Enterocutaneous fistula (EF) in newborns and prematures is a well-recognized complication after necrotizing enterocolitis and other abdominal surgical procedures. Conservative management consists of bowel rest, antibiotics, wound care, and the administration of drugs that either reduce gastrointestinal motility or secretions. Octreotide decreases gastrointestinal secretions, inhibits or blocks the effects of gastrointestinal hormones, diminishes gut motility and thus reduces the flow through the fistula. We used octreotide and were able to report successful spontaneous closure of a fistula in our 2 neonatal patients, one a premature neonate with necrotizing enterocolitis (NEC) and the other with meconium peritonitis.

Gastrointestinal growth factors and neoplasia

Gastrointestinal (GI) hormones are chemical messengers that have been recognized for over a century as regulatory factors for normal physiologic functions in the GI tract and pancreas, including absorption, secretion, motility, and digestion. These hormones traditionally act in a true endocrine fashion with release from a distant site to regulate physiologic functions of specific target organs. In general, GI hormones bind to their G-protein-coupled receptors (GPCRs) to produce their endocrine effects. In addition to effects on physiologic functions of the GI tract and pancreas, selected GI hormones can act in an endocrine, paracrine, and/or autocrine fashion to stimulate the proliferation of normal and neoplastic GI tissues as well as non-GI tissues. This review will focus on effects of GI hormones on neoplastic tissues concentrating on the hormones that have been best characterized for these effects.

Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach

Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7–36)amide 10 −8 and 10 −7 M decreased ghrelin secretion significantly. In contrast, GIP 10 −8 and 10 −7 M augmented not only prestimulated, but also basal ghrelin secretion ( p<0.05). Insulin reduced ghrelin at 10 −10, 10 −8 and 10 −6 M ( p<0.05). Both gastrin 10 −8 M and somatostatin 10 −6 M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7–36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.

Roles of gastrointestinal hormones in pancreatic cancer.

Several gastrointestinal (GI) hormones, such as gastrin, cholecystokinin, and bombesin, have been reported to affect the development of pancreatic cancer. The receptors for these hormones are found in normal and neoplastic pancreatic cells. Activation of these receptors enhances pancreatic carcinogenesis and promotes the growth of established pancreatic carcinoma either in vitro or in vivo. On the other hand, some studies have shown that these GI hormones may have no effect or may play an inhibitory role in the development of pancreatic cancer. The reasons for the apparent discrepancies in the published literature are discussed in this review. In recent years, increasing emphasis has been placed on the effects of GI hormones on cancer invasion and metastasis. As the transition from noninvasion to the invasive state is the crucial event in cancer development, further investigation of the way in which GI hormones affect the invasion and metastasis of pancreatic cancer may be important for the development of new therapeutic approaches with eventual clinical utility.

Effect of gastrointestinal hormones and synthetic analogues on the growth of pancreatic cancer.

The effects of hormones and synthetic analogues have been examined on the growth of 2 human pancreatic cancer cell lines, MiaPaCa2 a well-established cell line and PANI which was derived in our own laboratories from a tumour specimen. The hormones/growth factors included gastrin (G-17), epidermal growth factor (EGF) and bombesin, while the synthetic analogues used were a gastrin receptor antagonist (CR 1718), a somatostatin analogue (RC-160) and a bombesin receptor antagonist (ICI 216,140). Cell proliferation was assessed by the [75Se]selenomethionine uptake method which has been shown to correlate with cell counts. The effect of each hormone or growth factor on growth was expressed as a percentage of the untreated control. There were 5 replicates in each experiment, and each one was repeated at least 3 times. In vitro growth of both cell lines was unaffected by gastrin, bombesin or the respective antagonists (CR1718 and ICI 216140). The somatostatin analogue RC-160 also had no effect on basal growth. Significant growth stimulation of both MiaPaCa2 and PANI was seen with epidermal growth factor. We tested the hypothesis that somatostatin analogues may inhibit EGF-stimulated growth on both MiaPaCa2, a somatostatin receptor positive cell line, and on PANI which is negative for somatostatin receptors. RC-160 did not inhibit EGF-stimulated growth of either MiaPaCA2 or PANI. Both cell lines were established in vivo as xenografts in nude mice. The effect of RC-160 on tumour growth was measured. RC-160 inhibited the growth of MiaPaCa2, the somatostatin receptor-positive cell line, but not of PANI.

The effect of gastrointestinal hormones on the incorporation of tritiated thymidine in the pancreatic adenocarcinoma cell line (WD PaCa).

In view of the trophic action of gastrointestinal hormones on the exocrine pancreas, the effects of secretin, octapeptide of cholecystokinin (CCK-8), and desglugastrin on the growth of hamster pancreatic well differentiated adenocarcinoma were investigated in vitro. Desglugastrin exhibited the greatest effect on thymidine incorporation into these cells after a lag period of 96 h. Doses of desglugastrin in the range from 30 to 270 ng/mL caused a significant and dose-dependent increase in thymidine incorporation. Higher doses of this peptide led to a decreased response. Secretin also increased thymidine incorporation, but the response was less than that induced by gastrin. Prolonged incubation with secretin for 96 h increased tritiated thymidine incorporation in a log-dose fashion in the range of 30 to 270 ng/mL. Doses of CCK-8 in the range of 90 to 810 ng/mL significantly increased thymidine incorporation after 48 h of incubation. Following 72 h of incubation, only the dose of 270 ng/mL continued to exhibit a significant stimulation. Our study suggests that the gastrointestinal hormones could directly increase the growth of pancreatic carcinoma cells, act synergistically with endogenous growth factors, or stimulate the local production of these factors. In any event, our results that gastrin, secretin, and CCK can stimulate the growth of pancreatic ductal tumor cells in tissue cultures, support earlier findings on normal and malignant pancreatic parenchyma.

Effects of gastrointestinal hormones on the growth of human intestinal epithelial cells in vitro.

The growth of cultured epithelium like cells from human normal embryonic intestine was studied in response to various hormones using a method that quantifies the number of cells by the amount of dye that they bind after fixation. Gastrin and neurotensin in the pg/ml range and higher caused small increases in cell growth. Glucagon and VIP were stimulatory in the low ng/ml range, whereas somatostatin and bombesin had no effect at the lower concentrations but were stimulatory at the highest concentration tested (10 and 100 ng/ml respectively). Secretin and pancreozymin (cholecystokinin) seemed to be ineffective.

Differential effects of gastrointestinal hormones on the blood flow of the alimentary tract of the dog.

The blood flow of the alimentary tract in anesthetized dogs was measured with radioactively labeled 15-micron microspheres before and after i.v. application of the gastrointestinal hormones glucagon, vasoactive intestinal polypeptide (VIP), secretin, and somatostatin. After 5 min glucagon in a dose of 75 micrograms/kg bolus + 5 micrograms/kg X min-1 infusion increased significantly the blood flow in liver, stomach, duodenum, jejunum, ileum, and colon as well as the cardiac output by 160%, 761%, 662%, 576%, 817.3%, 320%, and 108%, respectively. A dose of 3 ng/kg X min-1 resulted in reduction of the circulation in liver, gastric fundus, duodenum, and colon by 27.7%, 19.1%, 16.2%, and 10.7% after 5 min while the cardiac output was not affected. Vasoactive intestinal polypeptide (VIP) infused in a dose of 3.3 pmol/kg X min-1 for 5 min increased the blood flow in the pancreas by 30% and reduced it in the spleen and gastric corpus by 26.9% and 41.5%, respectively. Secretin, another member of the glucagon family, after a 5-min infusion of a dose of 0.5 CU/kg X min-1 increased the cardiac output by 49.96% and the renal circulation by 120.7%. In the gastrointestinal tract circulation of the gastric antrum was stimulated by 474%, of the duodenum by 93.5% and of the ileal mucosa by 178%. Infusion of the pancreatic hormone somatostatin (3.5 micrograms/kg bolus followed by infusion of 3.5 micrograms/kg X h-1) increased the blood flow in the liver by 13%, in the pancreas by 23.15%, and in the spleen by 29.8%, while it reduced it in the fundic mucosa by 17.1% and corpus mucosa by 28.8%. In summary, the gastrointestinal hormones examined exert marked and distinct effects on the circulation of the gastrointestinal tract, each hormone in different parts of the digestive tract. Thus, the local microcirculation of the gastrointestinal tract seems to be subject to hormonal in addition to nerval control.

Effects of gastrointestinal hormones on Oddi's sphincter and duodenal myoelectric activity and pancreatobiliary pressure. Studies in the opossum.

Myoelectric activity of Oddi's sphincter and duodenum was correlated with common duct and pancreatic duct pressures in conscious opossums after infusion of the following substances: cholecystokinin, pentagastrin, glucagon, secretin, and acetylcholine. Cholecystokinin and pentagastrin increased and glucagon and secretin decreased the frequency of spike potentials in Oddi's sphincter and the duodenum. Acetylcholine was associated with the largest increase in spike potentials in both Oddi's sphincter and the duodenum. Although there was variation in the number of pressure elevations related to Oddi's sphincter spike potentials, the baseline pressure remained constant during administration of the hormones. Acetylcholine infusion increased the biliary and pancreatic pressures to 29 and 31 mm Hg, respectively. We conclude that gastrointestinal hormones may have an important role in regulating the excretion of bile and pancreatic juice into the duodenum.

Effect of gastrointestinal hormones on choleresis from the isolated perfused rat liver.

Using isolated perfused rat liver, the direct effect of secretin, glucagon, caerulein, insulin and somatostatin on choleresis was investigated. When the liver was perfused in the absence of sodium taurocholate, the bile volumes were: control, 0.33 +/- 0.01 (mean +/- S.E.M.) ml/10 g liver per 50 min; secretin 0.05 U/ml, 0.39 +/- 0.01 (P less than 0.01); glucagon 10(-10) M, 0.44 +/- 0.02 (P less than 0.01); caerulein 10(-8) M, 0.34 +/- 0.03 (n.s.); insulin 1 mU/ml, 0.35 +/- 0.02 (n.s.); glucagon plus somatostatin 10(-7) M, 0.46 +/- 0.03 (n.s. vs. glucagon alone), respectively. When 10(-5) M sodium taurocholate was present in the perfusate, the bile volumes were: control, 0.61 +/- 0.03; secretin, 0.63 +/- 0.01 (n.s.); glucagon, 0.70 +/- 0.01 (P less than 0.05); caerulein, 0.55 +/- 0.01 (n.s.); insulin, 0.62 +/- 0.04 (n.s.); somatostatin, 0.59 +/- 0.01 (n.s.); respectively. Glucagon increased glucose output and cyclic AMP in the effluent from the liver neither of which were suppressed by somatostatin. Secretin increased cyclic AMP but not glucose output. These results indicate that glucagon has the most potent action on bile acid-independent canalicular bile, that caerulein and insulin do not act on canalicular bile production directly and that somatostatin does not directly suppress canalicular bile production nor hepatic glucose output produced by glucagon in rats.

Effects of gastrointestinal hormones and their related compounds on gastric motility in the rat.

We examined the effects of certain gastrointestinal hormones on gastric motility using rat stomach preparatios in vivo. Changes of water level caused by the movement of the stomach which was filled with saline were recorded. Single injections of cholecystokinin (1, 2 and 4 micrograms/kg) induced relaxation of the stomach. Single injections of bombesin in low doses (below 0.2 microgram/kg) induced relaxation and in high doses (over 0.2 micrograms/kg) contraction after brief relaxation. Single injections of neurotensin (1, 2, 4 and 8 micrograms/kg), somatostatin (5, 10 and 20 micrograms/kg) and substance P (1, 2, 4 and 8 micrograms/kg) induced relaxation followed by contraction, but their dose-response relations were obscure. Infusions of neurotensin (1, 5 and 25 micrograms/kg/h) and somatostatin (2.5 and 5 micrograms/kg/h) enhanced the stomach tension, whereas substance P (1, 5 and 25 micrograms/kg/h) reduced it. Single injections and infusions of neurotensin, somatostatin or substance P showed different effects on gastric motility. On the other hand, Met-enkephalin (1, 10 and 100 micrograms/kg) and porcine motilin (1, 10 and 100 micrograms/kg) did not affect gastric motility in our rat stomach preparations. These results suggest that some gastrointestinal hormones take part in stomach movements.

Effects of gastrointestinal hormones on ileal vascular and visceral smooth muscle.

Blood levels of gastrin, secretin, gastric inhibitory polypeptide (GIP), and cholecystokinin octapeptide (CCK-8) increase after a meal and may affect vascular and/or visceral smooth muscle. To study this possibility, we measured the effects of local intra-arterial infusion of these hormones on ileal perfusion pressure and intestinal wall compliance. In pentobarbital sodium-anesthetized dogs, a segment of ileum was exteriorized and vascularly perfused at constant flow with arterial blood. Wall compliance was calculated from the pressure generated by incremental changes in intraluminal volume (delta V/delta P). Postprandial blood levels of these hormones did not affect ileal perfusion pressure. However, higher blood levels of secretin and GIP did significantly lower perfusion pressure. Wall compliance was significantly increased by postprandial blood levels of secretin and GIP, while postprandial blood levels of CCK-8 decreased compliance. Gastrin was without effect on compliance. These data suggest these hormones do not contribute to postprandial ileal hyperemia. However, secretin, GIP, and CCK-8 do affect the postprandial activity of ileal visceral smooth muscle.

Effect of gastrointestinal hormones and amines on intestinal motility and the migration of Hymenolepis diminuta in the rat small intestine

Mettrick D. F. and Podesta R. B. 1982. Effect of gastrointestinal hormones and amines on intestinal motility and the migration of Hymenolepis diminuta in the rat small intestine. International Journal for Parasitology 12: 151–154. The effect of oral and/or intravenous administration of the gastrointestinal hormones gastrin, secretin and cholecystokinin-pancreozymin, the amine serotonin, histamine and glucose on intestinal transit and the distribution of the tapeworm Hymenolepis diminuta in the rat intestine, were examined at 30-min intervals for up to 4 h. Oral and/or intravenous administration of the GI hormones, serotonin, histamine and glucose accelerated intestinal transit of the marker but, except for the smaller histamine-stimulated increase in the parasitised animals, no significant differences were evident between infected and uninfected intestines. Concomitant administration of Mg 2+ with serotonin inhibited the serotonin-induced increase in intestinal marker transit. With the exception of gastrin, administration of the hormones and of serotonin induced a proximal redistribution of parasites. Histamine resulted in a strong distal movement of the parasites. The serotonin induced a proximal migration and was inhibited by Mg 2+ The results suggest that parasite relocation in the intestine is not a response to any single luminal parameter but, rather, a reaction to a complex of changes in the pre- and post-prandial intestinal lumen which occur as part of the host's response to the physiological stimulus of a meal.

Effect of gastrointestinal hormones on the biliary sphincter of the opossum

The smooth muscle sphincter enveloping the terminal portion of the common bile duct in the opossum exhibits spontaneous electrical activity and simultaneous rhythmic contractions. The aim of our study was to define the influence of four gastrointestinal hormones on biliary sphincter electrical and mechanical activity. An array of five monopolar extracellular electrodes was placed along the opossum choledochal sphincteric smooth muscle and contiguous duodenum. A catheter in continuity with a pressure transducer, drop counter, and saline reservoir was placed in the common duct for simultaneous measurement of ductal pressure and flow. The cystic and distal common hepatic ducts were then ligated to isolate the common bile duct from the gallbladder and liver. In each opossum, biliary sphincteric and duodenal myoelectric activity, common bile duct and gallbladder pressure, and common duct flow were recorded simultaneously before and after the intravenous administration of five different doses of an enteric hormone. Ten animals were given 0.1–10.0 international dog units per kilogram body wt of cholecystokinin, 10 received 0.01–1.00 μg/kg body wt of cholecystokinin-octapeptide, 10 were given 0.1–10.0 μg/kg body wt of secretin, and 5 were given 0.1–10.0 μg/kg body wt of pentagastrin. Cholecystokinin, cholecystokinin-octapeptide, and pentagastrin all effected a significant increase in sphincter electrical spike activity and common duct pressure with a decrease in common duct flow. This contractile response was consistent at a wide range of hormonal levels. Secretin had little effect on biliary pressure, flow, and myoelectric activity. The data lend support to the concept that cholecystokinin and gastrin contract the biliary sphincter, metering bile flow at the time of gallbladder emptying in the opossum.

Effects of gastrointestinal hormones and carbamylcholine on cAMP accumulation in isolated pancreatic duct fragments from the rat.

A modification of a technique to isolate kidney tubule fragments and pancreatic acinar cells has been used to prepare a suspension of pancreatic duct fragments from rats with pancreatic lipomatosis due to pretreatment with penicillamine and a copper-free diet. This suspension is 90-95% pure almost without any acinar cell contamination. The accumulation of 3',5'-cyclic adenosine monophosphate (cAMP) in response to various gastrointestinal hormones, hormone-like substances and theophylline was studied in these isolated pancreatic duct fragments. In the absence of theophylline, secretin increased the level of cAMP in a dose-dependent manner with a maximum at 10(-6) M. With supramaximal doses the concentration of cAMP decreased. During maximal stimulation with secretin the level of cAMP was dependent on the concentration of fragments in the incubation mixture. Vasoactive intestinal peptide (VIP) also increased the formation of cAMP. However, VIP was 10 times less effective than secretin on a molar basis. The addition of various concentrations of VIP to a submaximal dose of secretin did not alter cAMP levels as compared to the levels observed with the same concentration of secretin alone. Theophylline (5 x 10(-3) and 10(-2) M) stimulated cAMP accumulation and 5 x 10(-3) M theophylline potentiated the response to secretin and VIP. Pancreozymin (20 and 99% pure), glucagon bovine pancreatic polypeptide and carbamylcholine did not effect the level of cAMP when given alone or in combination with secretin. These data lend support to the hypothesis that cAMP is the intracellular mediator of the action of secretin and VIP on the pancreatic duct cells.