ceruletide and Pancreatic-Fistula

Leptin released by adipocytes has been implicated in the control of food intake but recent detection of specific leptin receptors in the pancreas suggests that this peptide may also play some role in the modulation of pancreatic function. This study was undertaken to examine the effect of exogenous leptin on pancreatic enzyme secretion in vitro using isolated pancreatic acini, or in vivo in conscious rats with chronic pancreatic fistulae. Leptin plasma level was measured by radioimmunoassay following leptin administration to the animals. Intraperitoneal (i.p.) administration of leptin (0.1, 1, 5, 10, 20 or 50 microg/kg), failed to affect significantly basal secretion of pancreatic protein, but markedly reduced that stimulated by feeding. The strongest inhibition has been observed at dose of 10 microg/kg of leptin. Under basal conditions plasma leptin level averaged about 0.15 +/- 0.04 ng/ml and was increased by feeding up to 1.8 +/- 0.4 ng/ml. Administration of leptin dose-dependently augmented this plasma leptin level, reaching about 0.65 +/- 0.04 ng/ml at dose of 10 microg/kg of leptin. This dose of leptin completely abolished increase of pancreatic protein output produced by ordinary feeding, sham feeding or by diversion of pancreatic juice to the exterior. Leptin (10(-10)-10(-7) M) also dose-dependently attenuated caerulein-induced amylase release from isolated pancreatic acini, whereas basal enzyme secretion was unaffected. We conclude that leptin could take a part in the inhibition of postprandial pancreatic secretion and this effect could be related, at least in part, to the direct action of this peptide on pancreatic acini.

Topics: Animals; Bethanechol Compounds; Ceruletide; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Therapy, Combination; Eating; Gastric Fistula; Injections, Intraperitoneal; Leptin; Pancreas; Pancreatic Fistula; Pancreatic Juice; Postprandial Period; Rats; Rats, Wistar

Stimulation of pancreatic sensory nerves by capsaicin produced secretory effects probably caused, at least in part, by the release of CGRP.. In the pancreas calcitonin gene-related peptide (CGRP) has been localized in the sensory nerves, but its physiological role is unknown. This study was undertaken to compare the changes of pancreatic enzyme secretion produced by CGRP and by stimulation or destruction of sensory nerves.. To stimulate sensory nerves, low doses of capsaicin (0.25-0.5 mg/kg) were given intraduodenally to the conscious rats with chronic pancreatic fistula. To inactivate sensory nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10 d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and capsaicin-denervated rats.. In conscious rats, CGRP given subcutaneously (5-10 micrograms/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic secretion. In isolated pancreatic acini, CGRP (10(-10)-10(-6) M), but not capsaicin, increased basal or secretagog-stimulated amylase release. In pancreatic slices (containing nerve fibers) capsaicin (10(-10)-10(-6) M) increased enzyme secretion, and this secretion was abolished by previous inactivation of sensory nerves by this neurotoxin. Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory denervation by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic juice to the exterior during first 2 h of the tests.

Topics: Amylases; Animals; Bethanechol Compounds; Calcitonin Gene-Related Peptide; Capsaicin; Ceruletide; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Neurons, Afferent; Pancreas; Pancreatic Fistula; Rats; Rats, Wistar; Time Factors

We measured bicarbonate and protein secretory responses to graded doses of intravenous caerulein and bethanechol and intraduodenal L-phenylalanine alone or with background secretin; graded doses of secretin alone or with background caerulein or L-phenylalanine; and background secretin plus graded doses of caerulein or L-phenylalanine plus background atropine sulfate. Potentiation (more-than-additive response) occurred for bicarbonate secretion between secretin and caerulein, between secretin and L-phenylalanine, but not between secretin and bethanechol. The only potentiating interaction for protein secretion was between secretin and low doses of caerulein. Atropine abolished the potentiated bicarbonate response to secretin plus L-phenylalanine but had no effect on the response to secretin plus caerulein. Potentiation between secretin and cholinergic mechanisms and cholecystokinin for pancreatic bicarbonate secretion may be an important regulatory mechanism, while potentiation of protein secretion with these stimulants does not appear to be important in dogs. A cholinergic mechanism mediates much of the bicarbonate potentiation between secretin and intestinal L-phenylalanine.

Topics: Animals; Atropine; Bethanechol; Bethanechol Compounds; Bicarbonates; Ceruletide; Dogs; Drug Synergism; Gastric Fistula; Pancreas; Pancreatic Fistula; Phenylalanine; Proteins; Secretin; Stimulation, Chemical

The effects of various doses of synthetic neurotensin on exocrine pancreatic secretion were investigated in dogs prepared with pancreatic fistulae. Increasing doses of neurotensin infused intravenously caused a dose-dependent stimulation of exocrine pancreatic secretion. Plasma neurotensin levels determined with a radioimmunoassay kit for neurotensin were significantly correlated to the amount of neurotensin infused. Significant stimulation of exocrine pancreatic secretion was observed when 2.5 pmol kg-1 min-1 neurotensin were infused. This dose resulted in neurotensin plasma levels comparable to those observed after a meal. Combined infusions of neurotensin and the cholecystokinin analogue cerulein had synergistic effects on pancreatic bicarbonate output and raised the HCO-3:protein ratio. These observations suggest that neurotensin may play a role in the early phase of postprandial stimulation of exocrine pancreatic function.

Topics: Animals; Bicarbonates; Ceruletide; Dogs; Dose-Response Relationship, Drug; Neurotensin; Pancreas; Pancreatic Fistula; Pancreatic Juice; Radioimmunoassay; Stimulation, Chemical

Pancreatic volume flow as well as bicarbonate and protein secretion have been measured in chronic pancreatic fistula cats and dogs in response to I.V. infusion of VIP and secretin or duodenal perfusion of sodium oleate and HCl solution. 2. VIP and secretin infused I.V. in cats produced superimposable pancreatic dose-response curves for volume flow and bicarbonate secretion, reaching almost identical observed and maximal calculated outputs with both peptides. In dogs, VIP was shown previously to be a much less effective stimulant of pancreatic secretion than secretin and the maximal observed bicarbonate output in response to VIP was only about 17% of that to secretin (Konturek, Thor, Dembinski & Król, 1975). It is condluded that VIP in cats is a secretin-like full agonist, whereas in dogs it is a partial agonist of pancreatic bicarbonate secretion. 3. In cats, secretin and VIP showed equal efficacy and their combination exhibited an augmentatory action on pancreatic bicarbonate secretion with additive kinetics, whereas in dogs, VIP was found to have a lower efficacy than secretin and to inhibit competitively secretin-induced pancreatic secretion. These results might be explained by the interaction of VIP and secretin, two chemically related peptides, on a common receptor site of the exocrine pancreas. 4. Caerulein, an analogue of CCK-PZ, infused I.V. in cats and dogs caused a negligible pancreatic bicarbonate secretion and a potent dose-dependent protein secretion. The combination of graded doses of VIP or secretin with a background dose of caerulein resulted in significantly higher bicarbonate and protein outputs than those induced by VIP or secretin alone. 5. Duodenal perfusion of sodium oleate soap in cats and dogs produced pancreatic dose-response curves for volume flow and bicarbonate output similar to those evoked by VIP in these species. Pancreatic protein secretion in response to luminal oleate was slightly higher than could be accounted for by the action of VIP alone. This might be attributed to the release by oleate not only of endogenous VIP but also CCK-PZ or to the vago-vagal reflexes from gut to pancreas. The results of our combined study on cats and dogs suggest the possibility that oleate releases VIP from the gut and that this peptide may play a physiological role in the stimulation of pancreatic secretion.

Topics: Animals; Bicarbonates; Cats; Ceruletide; Dogs; Dose-Response Relationship, Drug; Gastrointestinal Hormones; Hydrochloric Acid; In Vitro Techniques; Oleic Acids; Pancreas; Pancreatic Fistula; Peptides; Proteins; Secretin; Stimulation, Chemical

Vasoactive inhibitory peptide (VIP) and secretin were compared in regard to the stimulation of pancreatic bicarbonate secretion and the augmentation of pancreatic response to caerulein or a peptone meal in chronic gastric and pancreatic fistula dogs. Dose-response analysis showed that maximal bicarbonate response to VIP was about 17% of that to secretin. Both caerulein and endogenous cholecystokinin, released by a peptone meal, clearly potentiated pancreatic bicarbonate response to VIP in a manner similar to secretin. The interactions of these two peptides showed that VIP is a potent inhibitor of secretin-induced pancreatic secretion. From the dose-response curves to secretin alone and secretin plus VIP, Michaelis-Menten analysis showed typical competitive inhibition, which indicates that VIP and secretin share a common receptor site.

Topics: Amylases; Animals; Bicarbonates; Ceruletide; Cholecystokinin; Depression, Chemical; Dogs; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Gastric Fistula; Gastrointestinal Hormones; Infusions, Parenteral; Kinetics; Pancreas; Pancreatic Fistula; Pancreatic Juice; Peptides; Peptones; Proteins; Secretin

Topics: Animals; Bethanechol Compounds; Ceruletide; Cholecystokinin; Dogs; Dose-Response Relationship, Drug; Gastric Fistula; Gastrointestinal Agents; Histamine; Pancreas; Pancreatic Fistula; Peptides; Proteins; Secretory Rate; Stimulation, Chemical; Stomach; Vagotomy

Topics: Animals; Bicarbonates; Bile; Biliary Fistula; Ceruletide; Dogs; Dose-Response Relationship, Drug; Duodenum; Gastric Fistula; Hydrogen-Ion Concentration; Ileum; Jejunum; Liver; Meat; Pancreas; Pancreatic Fistula; Pancreatic Juice; Phenylalanine; Secretin; Secretory Rate; Taurocholic Acid; Tryptophan

Topics: Animals; Bethanechol Compounds; Ceruletide; Cholecystokinin; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrointestinal Agents; Leucine; Pancreas; Pancreatic Fistula; Pancreatic Juice; Pentagastrin; Peptides; Stomach; Tryptophan

Topics: Animals; Bicarbonates; Cats; Ceruletide; Drug Interactions; Gastric Fistula; Gastric Juice; Gastrointestinal Hormones; Histamine; Histamine Antagonists; Kinetics; Pancreas; Pancreatic Fistula; Pentagastrin; Peptic Ulcer; Peptides; Stomach