Intravenous Secretin Research Articles

Secretin-stimulated trypsin-like immunoreactivity in alcoholics

Serum trypsin-like immunoreactivity (TLI) was studied in alcoholics without evidence of pancreatic disease and in controls. Basal values were 29 ± 4.6 μg/l (mean ± S.E.M) in alcoholics and 23 ± 4.4 μg/l in controls ( p not significant). The injection of secretin was followed by a significant increase of serum TLI in both groups; the integrated trypsin output (ITO) in the first hour after secretin administration was 947 ± 403 (mean ± S.E.M.) in alcoholics and 76 ±15 in controls ( P < 0.05). In 9 (75%) of the alcoholics tested, ITO was higher than the highest ITO of controls. The increase of serum TLI after injection of secretin is probably due to secretion and/or regurgitation of trypsinogen into the bloodstream when the pancreas is stimulated with intravenous secretin. In the light of experimental studies on chronic ethanol intoxication in animals, the increased ITO observed in alcoholics may suggest obstruction to pancreatic secretory flow in spite of the absence of any clinical sign of pancreatic disease.

Elevated serum levels of pancreatic secretory proteins in cigarette smokers after secretin stimulation.

The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.

Relationship between plasma pH and pancreatic HCO3- secretion at different intravenous secretin infusion rates.

The relationship between pancreatic HCO3- secretion and plasma pH during acute systemic acid-base changes was investigated in 6 anesthetized, artificially ventilated pigs (20-25 kg) at 2 different, i.v. secretion infusion rates. At 0.45 C.U./kg b. wt. h-1 secretin infusion and plasma pH 7.40 +/- 0.01 pancreatic HCO3- secretion averaged 61+/- 12 mumol/min. Stepwise lowering of plasma pH through i.v. infusion of HCl and CO2 administration to inspired air proportionately reduced secretion rate; estimated zero HCO3- secretion occurring at plasma pH 7.01. Subsequent i.v. secretin infusion at 2.70 C.U./kg b. wt. h-1 increased HCO3- secretion to 249 +/- 42 mumol/min at plasma pH 7.33 + 0.04; stepwise lowering of plasma pH proportionately reduced HCO3- secretion to estimated zero at plasma pH 6.71. A reduction of plasma pH by 0.1 pH unit reduced HCO3- secretion during low and high rate of i.v. secretin infusion by 18 +/- 3 mumol/min and 35 +/- 8 mumol/min, respectively. Secretin infusion rate did not affect pancreatic chloride excretion. These findings support the view that secretin increases HCO3- secretion, and hence proton transport to the interstitial fluid, by augmenting the proton motive force developed by HCO3- secreting cells.

Exogenous and endogenous stimulations during different phases of pancreatic secretion in conscious rats

The effects of stepwise increasing doses of intravenous caerulein, secretin, urecholine and intraduodenal oleic acid were investigated in conscious rats. a) Basal water, bicarbonate, and protein secretion significantly augmented after diversion of pancreatic juice. On the basis of protein secretory pattern of basal secretion 3 stable stages have been recognised: 1. The most physiological basal stage during return of pancreatic juice. 2. The first, highly elevated plateau from the 4th to 7th 30-min period after diversion of pancreatic juice. 3. The second, delayed and less elevated plateau after 270 min. b) The following patterns of stimulated secretion were observed: 1. Caerulein stimulated protein and bicarbonate secretion during return of juice and the first plateau but it failed to elicit a significant response during the second, delayed plateau. 2. Secretin and urecholine showed similar protein responses during return of pancreatic juice but after diversion, they stimulated water and bicarbonate secretion only. 3. During the second plateau oleic acid stimulation resulted in a significant increase in water and bicarbonate secretion but no significant increase occured in protein output. The delayed inhibition of protein secretion, previously described in our laboratory, was unchanged. 4. Supramaximal doses of exogenous stimuli caused an inhibition in pancreatic secretion.

Serum Group I Pepsinogens During Prolonged Infusion of Pentagastrin and Secretin in Man

Six 20- to 25-year-old healthy men were studied with an intravenous pentagastrin infusion in a dose of 6 micrograms/kg-h for 4.5 h. Four of these were also studied on separate days with an intravenous secretin infusion in a dose of 2 CU/kg-h for 4.5 h. Gastric juice was collected continuously for one 30-min period before and in 30-min periods throughout the infusion periods, and the gastric H+ and pepsin outputs were determined during the pentagastrin infusion only. Blood was drawn before, every 30 min throughout the infusion, and the next morning for determination of serum group I pepsinogens (PG I), serum gastrin, and plasma secretin. Pentagastrin evoked a sustained rise in gastric H+ and pepsin secretions, a more delayed and sustained increase in serum PG I in the four subjects with a normal pentagastrin-stimulated maximal gastric secretion, and a fall in serum PG I in the remaining two subjects with a low gastric secretion. Secretin also elicited a sustained elevation in serum PG I in all four examined, including one who showed a fall in serum PG I during pentagastrin infusion. It is proposed that pentagastrin may exert its stimulatory effect of pepsinogen synthesis subsequent to degranulation of the chief cells, whereas secretin may stimulate the pepsinogen synthesis more directly. Thus, the fall in serum PG I during pentagastrin infusion in the two subjects with low gastric secretion may possibly be due to a defective cellular storage of PG I in atrophic gastritis. Plasma secretin was not affected by gastric suction or by prolonged infusion of pentagastrin, whereas serum gastrin fell during secretion infusion accompanied by gastric suction.

Biliary Mannitol Clearance and Bile Salt Output Before and During Secretin Choleresis in the Dog

The clearance of 14C-mannitol in the bile before and during intravenous secretin was measured in anesthetized dogs receiving a constant infusion of taurocholate. During secretin, bile flow (+80%) and bicarbonate output (+140%) both rose while bile salt output was unchanged (+2.4%). Mannitol clearance increased significantly by 20 +/- 8% (P less than 0.05). The ratio of bile salt output to mannitol clearance fell significantly after secretin by 14 +/- 7% (P less than 0.01). Secretin caused, therefore, a significant rise in mannitol clearance in this canine preparation. This may be due either to a rise in the bile salt independent fraction of canalicular bile or to tubular entry of mannitol.

Xylocaine treatment in experimental pancreatitis in pigs.

Experimental haemorrhagic pancreatitis was induced in 12 piglets by infusing Nataurocholate trypsin into the pancreatic duct with simultaneous intravenous secretin stimulation. Within some minutes after the infusion all animals developed severe pancreatitis accompanied by the production of bloody ascites. Unless given specific treatment the pigs died within 24 h. Of the animals treated with xylocaine infusion (50 microgram/kg/min for 24 h) one died within 24 h, one during the second day, and four lived for over a week, at which time they were killed. Although xylocaine treatment signficantly improved the survival of the animals, it did not seem to influence the local damage of the pancreatic tissue. Xylocaine has been shown to inhibit phospholipase-A in vitro. It is possible that xylocaine also acts in vivo by inhibiting phospholipase-A, thus preventing lethal tissue damages at an early stage of pancreatitis.

The effect of intestinal hormones on splanchnic circulation.

The influence of acidification of the duodenal contents, of intravenous secretin, cholecystokinin and pancreozym injections on hepatic (HAF) and left gastric artery (GAF) and on portal vein blood flow (PVF), bile and pancreatic juice output was studied in dogs. Acid introduction into the duodenum increased HAF and PVF by 20 and 25 percent, respectively. GAF did not change significantly. Secretin and cholecystokinin also increased PVF by 25 percent but HAF changes were less than after acidification. Pancreozym increased significantly only HAF. There were also differences between the effects of duodenal acidification and of the individual hormones on bile and pancreatic juice excretion. It is concluded, that splanchnic circulatory changes observed following duodenal acidification are not produced by the action of a single intestinal hormone but are due to the interplay of several factors.

Calcium and secretin as provocative stimuli in the Zollinger-Ellison syndrome.

The effects of calcium and secretin were studied in 8 patients with the Zollinger-Ellison syndrome and 18 patients with duodenal ulcer disease. Intravenous infusion of calcium gluconate produced marked increases in serum gastrin levels in the patients with Zollinger-Ellison syndrome (4,350 +/- 1,625 pg/mg) and very slight increases in the patients with duodenal ulcer disease (140 +/- 49 pg/ml). Secretin given as a single intravenous injection also induced marked elevations in serum gastrin in the group with the Zollinger-Ellison syndrome (4,063 +/- 1,990 pg/ml). By contrast, intravenous secretin resulted in a progressive fall in serum gastrin levels in the duodenal ulcer group (from 119 to 97 pg/mg). These results suggest that both stimuli are very useful dagnostic tools in discriminating between Zollinger-Ellison and non-Zollinger-Ellison patients. The secretin challenge test is felt to be superior to the calcium infusions because it is simpler, safer and very rarely produces false-negative or-positive results.

Gastrointestinal myoelectrical activity in idiopathic intestinal pseudo-obstruction.

We evaluated the myoelectrical and motor function of the esophagus, small intestine, colon and anal sphincter in four patients with chronic idiopathic intestinal pseudo-obstruction. All patients had aperistalsis of the esophagus, with incomplete relaxation of the lower esophageal sphincter after swallowing or balloon distension. Duodenal slow-wave frequency was normal at 11.4+/-0.3 (+/-S.E.M.) cycles per minute. The patients did not have a normal increase in duodenal spike or motor activity after intestinal distension, but duodenal activity increased after stimulation with intravenous secretin. Colonic slow-wave activities were present at two frequencies, 6.2+/-0.3 and 3.3+/-0.1 cycles per minute. Neostigmine administration increased both colonic spike and motor activity normally. These studies suggest that in this disorder, physiologic neural responses to swallowing or intestinal distension are impaired but the intestinal smooth-muscle slow-wave activity and the spike and motor responses to exogenous neurohormonal stimulation are intact.

Plasma secretin concentration and pancreatic exocrine secretion after intravenous secretin or intraduodenal HC1 in anaesthetized pigs.

The concentration of immunoreactive secretin in arterial blood and the exocrine pancreatic secretion were measured during intraportal infusion of secretin in doses of 0.03, 0.06, 0.1 and 3.0 clinical units kg-1 h-1, and during intraduodenal instillation of 50 ml 0.1 mol 1(-1) HC1. The lowest dose of exogenous secretin to significantly increase secretin concentration in blood was 0.03 clinical units kg-1 h-1, which was a subthreshold dose of exocrin pancreatic secretion. A linear relation was found between the dose secretin and the secretin concentrations measured. On the basis of secretin concentrations, release of secretin during instillation of HC1 was estimated to be 0.22 clinical units kg-1 h-1. Maximum pancreatic bicarbonate secretion was obtained with a dose of 1.0 clinical units kg-1 h-1, and the minimal effective dose was between 0.06 and 0.1 clinical units kg-1 h-1. On the basis of the flow rate of pancreatic juice and the pancreatic bicarbonate output, secretin during instillation of HC1 was estimated to be 0.3 clinical unit kg-1 h-1. It is concluded that the radioimmunoassay used has the sensitivity and accuracy necessary for measurements of secretin concentrations in plasma during physiological conditions.

Effects of Intravenous Secretin and Cholecystokinin on Gallbladder Net Water Absorption and Motility in the Cat

A perfusion technique has been used for the simultaneous study of the concentrating mechanism and the motility of the gallbladder in the anesthetized cat. It was found that intravenous secretin abolished the net water absorption from bile in the gallbladder and thereby impeded its concentrating mechanism, but alone did not influence gallbladder motility. It was sometimes seen that secretin even reversed the net water transport in the gallbladder, producing a secretion. Intravenous cholecystokinin was found not to influence the net water transport but to induce a strong contraction of the gallbladder. These results are discussed in relation to those from earlier in vitro studies.

Effect of methylated PGE2 analogs given orally on pancreatic response to secretin in man.

The effect of two methylated PGE2 analogs given orally on the pancreatic response to intravenous secretin has been studied in 8 healthy subjects. The secretion of bicarbonate was not changed by these PGE2 analogs. The secretion of enzymes during infusion of PGE2 analogs was significantly greater than in the control.

Lower Esophageal Sphincter in Reflux Esophagitis

Lower esophageal sphincter pressure (LESP) was studied by intraluminal perfusion-manometry in the resting state and after graded intravenous doses of pentagastrin in 12 healthy subjects and 27 patients with reflux esophagitis. These patients were classified as having ulcerative (11) or non-ulcerative esophagitis (16) by histological examination and endoscopic appearance of the inflamed mucosa. The length of the LES was similar in patients and controls. A correlation was found between the magnitude of mean basal end-expiratory (mbe) LESP reduction and the grade of esophageal mucosa inflammation. The most reduced mbe LESP value was shown in patients with ulcerative esophagitis. It was significantly different from that of patients with non-ulcerative esophagitis (t = 3.37, p less than 0.01). Both values were significantly reduced from that of the controls (t larger than or equal to 0.0125). The responsiveness of the LES to intravenous pentagastrin was quantitatively reduced throughout the whole range of the dose-response curve in patients with ulcerative esophagitis, whereas patients with non-ulcerative esophagitis only differed in the maximum mbe pressure value from the controls. Four patients showed a paradoxical pressure decrease to intravenous pentagastrin, resulting in a LESP reduction to 8% of the mbe LESP. Intravenous secretin or CCK led to a similar reaction of the LES in these patients.

Canine pancreatic response to intestinally perfused oligopeptides.

Although older work indicated that luminal peptides are stimulants of pancreatic secretion, these earlier experiments were performed with crude peptide mixtures containing amino acids that are also known stimulants. Furthermore, no information was provided about size or composition of stimulating peptides. For this reason, the problem was reinvestigated with commercially synthesized oligopeptides in dogs equipped with chronic gastric and pancreatic fistulas. Synthetic peptides at 30 mM concentrations were perfused into the proximal bowel when luminal pancreatic proteases were reduced to undetectable concentrations and dogs were receiving intravenous exogenous secretin infusions. Increases in pancreatic outputs of protein and bicarbonate were measured. Of the peptides tested, only glycylphenylalanine, glycyltryptophan, and phenylalanylglycine stimulated, whereas both di- and triglycine were without effect. It was concluded that some, but not all, oligopeptides in the gut lumen are stimulants of pancreatic secretion.

Exocrine pancreatic function in juvenile-onset diabetes mellitus.

Exocrine pancreatic function was studied in 20 juvenile-onset diabetics, seven maturity-onset diabetics, and five patients with diabetes secondary to chronic pancreatitis. The results were compared with 13 non-diabetic controls. The outputs of bicarbonate, trypsin, and amylase were reduced in the diabetic patients in response to intravenous secretin and CCK-PZ. In the juvenile-onset group, exocrine pancreatic secretory capacity was reduced in 80% of the patients, and the severity of the reduction was related to the duration of the diabetes. The reduction in pancreatic secretory capacity must be taken into consideration when interpreting pancreatic exocrine function in patients with diabetes.

Canine gut receptors mediating pancreatic responses to luminal L-amino acids

Pancreatic protein and bicarbonate outputs were measured in dogs with pancreatic fistulas receiving intravenous secretin while individual L-amino acids or mixtures of L-amino acids were perfused into proximal intestine, Both phenylalanine and tryptophan were potent stimuli of pancreatic secretion; alanine, leucine, and valine increased protein outputs but their effects were small and not statistically significant. Six other amino acids were ineffective. Tryptophan perfused together with phenylalanine augmented responses to phenylalanine; methionine, ineffective when perfused alone, did not alter responses to phenylalanine when perfused with the latter. Responses to phenylalanine perfused at concentrations above 8 mM were dependent on load and were mediated by lengths of proximal bowel greater than 10 cm.

Cyclic Amp in Secretin Choleresis

Cyclic AMP output in the bile in response to intravenous secretin was measured in 11 patients, 12 baboons, and 15 dogs. Secretin was given to patients with bile drainage tubes as an intravenous bolus (1 U per kg). In baboons and dogs both secretin infusion (4 U per kg per hr) and bolus injection (1 U per kg) were used. In baboons cyclic AMP was also determined in liver, extrahepatic duct tissue, and in perfusate from isolated segments of extrahepatic bile ducts. Secretin induced a marked choleresis in all three species. In humans, biliary cyclic AMP concentration increased an average (+/- 1 SE) of 68% +/- 12% and in baboons 4-fold, but no increase occurred in dogs. In baboons, cyclic AMP concentration increased in both bile duct tissue and perfusate from isolated bile ducts concomitant with secretin choleresis, but not in liver. In humans the choleretic effects of sodium dehydrocholate, aminophylline, and glucagon were compared to dibutyryl cyclic AMP (DBcyclic AMP). All agents increased bile flow 2- to 3-fold. Cyclic AMP concentration in bile markedly increased after glucagon and DBcyclic AMP but not after sodium dehydrocholate and aminophylline. We conclude that cyclic AMP is implicated in secretin choleresis in both humans and baboons, but not in dogs. The bile duct appears to be the site of cyclic AMP elaboration induced by secretin in baboons and probably is also in man.

Letter: Zollinger-Ellison syndrome: calcium, secretin, gastrin.

Excerpt To the editor: In a recent issue Kolts, Herbst, and McGuigan ( 1 ) report on having administered intravenous calcium and secretin to 3 patients with the Zollinger-Ellison syndrome; they con...

Release of cholecystokinin by acid (38562).

In dogs with pancreatic fistulas, the amount of CCK released by acid in the intestine was estimated by determining how much exogenous CCK had to be fiven to mimic the pancreatic protein response. Duodenal infusion of 16 mmole/hr of HCl with a high background dose of intravenous secretin stimulated pancreatic protein secretion to about the same degree as 0.5 unit/kg-hr of exogenous CCK; the same acid load without secretin background gave a response equivalent to about 0.7 unit/kg-hr of CCK. Expressed as fractions of their respective doses for half maximal response, acid releases almost five times more secretin than CCK.