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At least 19 recordsLinked to original sources
PubMed1979

Physiological significance of secretin in the pancreatic bicarbonate secretion. II. Pancreatic bicarbonate response to a physiological increase in plasma secretin concentration.

The pancreatic response to physiological concentrations of secretin obtained after minute boluses of exogenous secretin was studied in 16 normal volunteers. Output of bicarbonate into the duodenum was measured by duodenal aspiration in 5 subjects and by endoscopic cannulation of the pancreatic duct in 11 subjects. Pure natural porcine secretin was injected intravenously in doses of 125, 250, and 500 fmol x kg-1 body weight (0.0013, 0.0027, and 0.0054 clinical units x kg-1). All three doses of secretin increased plasma secretin concentration, duodenal bicarbonate concentration, and duodenal bicarbonate output significantly. The bicarbonate output measured by the two techniques did not differ significantly. The increments in median plasma secretin concentration were 1.6, 3.0, and 6.4 pmol x 1(-1) after secretin, 125, 250 and 500 fmol x kg-1, and the corresponding 15-min bicarbonate output 283, 442, and 1435 micromol, respectively. The concentrations of secretin in plasma found after these doses of secretin are of the same order of magnitude as the secretin concentrations found during physiological conditions in man. It is concluded that the physiological concentrations or secretin influence pancreatic bicarbonate secretion.

Bicarbonates↗
PubMed1979

Physiological significance of secretin in the pancreatic bicarbonate secretion. I. Responsiveness of the secretin-releasing system in the upper duodenum.

In nine normal subjects intraduodenal pH was measured by means of a glass electrode placed in the passage from the first to the second part of the duodenum. The physiological variations in pH were simulated by intraduodenal injection of 2.5, 5, or 10 ml of 0.1 mol x 1(-1) HCl and subsequent neutralization by injection of bicarbonate. A total of 26 injections of acid was followed by a pH spike from a median pH of 7.0 to a median of pH 2.1 Median spike duration was 45 sec. The concentration of secretin in plasma increased from a median of 1.2 pmol x 1(-1) to a peak value of 2.2 pmol x 1(-1) after 4 min. It is concluded that the secretin response to a brief acidification of the first 4--6 cm of the duodenum is sufficient to explain the physiological variations in the concentration of secretin in human plasma.

Bicarbonates↗
PubMed1976

Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3':5'-monophosphate.

Secretin and vasoactive intestinal peptide (VIP), but not glucagon, stimulate accumulation of cyclic AMP in dispersed guinea pig pancreatic acinar cells. Secretin stimulated cellular accumulation of cyclic AMP by interacting with a single class of high affinity receptors. On the other hand, the dose-response curve for VIP-stimulated cellular cyclic AMP was biphasic and reflected interaction of this peptide with two classes of receptors. Results obtained with synthetic fragments of VIP and secretin indicate that the receptor having a high affinity for VIP has a low affinity for secretin, interacts with, but does not distinguish among, secretin, secretin 5-27 and [6-tyrosine] secretin or among secretin 14-27, VIP 14-28, VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, but not when occupied by secretin, [6-tyrosine] secretin, or secretin 1-14. The receptor having a low affinity for VIP has a high affinity for secretin, interacts with and distinguishes among secretin, secretin 5-27, and [6-tyrosine] secretin, interacts with secretin 14-27 but not with VIP 14-28 or VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, secretin, [6-tyrosine] secretin, or secretin 1-14.

Animals↗
PubMed1975

Effect of glucagon on secretin-stimulated bile flow.

The effect of glucagon on secretin-stimulated bile flow was evaluated in dogs with chronic biliary and gastric fistulas. Evaluation of the effects of secretin and glucagon alone on hepatic bile flow indicated that the calculated maximal response (CMR) values of the two agents were similar. Secretin increased the bicarbonate concentration in hepatic bile whereas glucagon did not, suggesting basic differences in mechanism of action. Administration of glucagon to secretin-stimulated bile flow produced an increase in bile flow while decreasing the bicarbonate concentration in secretin-stimulated bile. Since the maximal response for bile flow to glucagon and secretin was significantly greater than the maximal response to either agent alone, glucagon produced potentiation of secretin-stimulated bile. Glucagon increased the CMR value of secretin-stimulated bile from 513 mul/min for secretin alone to 692 mul/min for secretin and glucagon. This was associated with no significant change in the values of the respective D50S. These data suggest that glucagon produced a noncompetitive augmentation of secretin-stimulated bile flow and suggest that the two agents do not utilize the same receptor to stimulate bile flow.

Animals↗
PubMed1976

Observations of plasma secretin levels by radioimmunoassay in response to duodenal acidification and to a meat meal in humans.

The endogenous release of secretin in healthy human subjects was studied by measuring plasma secretin levels by radioimmunoassay (RIA) before, during, and following duodenal acidification and eating a meal. The sensitivity of our RIA was assessed by measuring plasma secretin levels during constant intravenous infusions of 4 graded doses of secretin. Our RIA detected significant increases (P less than 0.001) in plasma secretin with each dose, including a low dose of 0.125 U (41.3 ng)/kg hr. Intraduodenal infusion of 0.1 N HCl resulted in marked increases (P less than 0.001) in plasma secretin levels whenever pH in the second portion of the duodenum was reduced to less than 3.5. In contrast, following a meal, pH in the second portion of the duodenum remained consistently greater than 4.5 and plasma secretin levels showed no changes from basal levels. These studies confirm that endogenous release of secretin depends on an acidic pH of the duodenum, and insigificant changes in the plasma secretin level following ingestion of a meal suggest that endogenous release of secretin in the postprandial period is probably to small in quantity to be detected by the present radioimmunoassay method.

Adolescent↗
PubMed1978

Effect of chronic pentagastrin, cholecystokinin, and secretin on pancreas of rats.

Pentagastrin (1.5 mg/kg), 20% pure natural cholecystokinin (CCK, 37.5 Ivy dog U/kg) or secretin (25 microgram/kg) was given in a depot carrier subcutaneously to rats 3 times daily for 15 days. The dose of CCK and secretin was submaximal for pancreatic secretion, whereas the dose of pentagastrin was supramaximal for gastric acid secretion. The pancreatic wet weight increased by 12% (P less than 0.01) in the rats treated with pentagastrin, 57% (P less than 0.001) in those treated with CCK, and 9% (P less than 0.01) in those treated with secretin. In CCK-treated rats, the maximal protein and bicarbonate outputs in response to cholecystokinin increased proportionately to the increase in pancreatic weight, but maximal bicarbonate and protein outputs in response to secretin were unaltered. The secretin-treated rats showed a lowered basal secretion of bicarbonate and a lowered sensitivity to secretin stimulation, but the maximal bicarbonate and protein outputs to secretin and CCK were unchanged. Treatment with pentagastrin produced no significant changes in pancreatic responses to secretin or CCK. We conclude that 1) the increase in pancreatic weight produced by repeated injections of cholecystokinin was accompanied by proportional increase in functional capacity as reflected by the increased maximal bicarbonate and protein outputs in response to cholecystokinin, and 2) repeated administration of secretin decreased the sensitivity of the pancreas to secretin without altering maximal bicarbonate response.

Animals↗
PubMed1978

Uneven and transient secretin release after a liquid test meal.

In order to test the hypothesis that secretin may be released intermittently after feeding, the plasma secretin concentration was measured at short intervals, and the duodenal pH continuously recorded, after a liquid test meal in 10 human subjects. Secretin was measured with a radioimmunoassay in which the entire molecule is specifically recognized and the immunoreactivities of human secretin and of the porcine peptide used as standard are similar. In the total group, no significant variation of the mean plasma secretin concentration above basal was observed within 45 min after feeding. Analysis of the individual patterns revealed that secretin was released transiently in 5 of the 10 subjects, namely those showing variations of the duodenal pH down to or below 4.0 at some time after the meal. The mean peak delta secretin in these subjects was 7.2 pg ml-1 of plasma. In 7 additional subjects, bolus intravenous injections of 0.005 and 0.01 clinical units kg-1 of porcine secretin resulted in peak delta secretin concentrations of 5.5 and 10.5 pg ml-1, respectively, and were followed by a significant increase of bicarbonate output in the duodenal aspirate. These results indicate that secretin is released unevenly and intermittently in the early period after a liquid meal in man, in amounts that seem sufficient for the initiation of a significant bicarbonate response.

Adult↗
PubMed1978

Immunoreactive secretin in gastrointestinal mucosa of several mammalian species.

Immunoreactive secretin in hydrochloric acid extracts is relatively constant in the duodenum and proximal jejunum of pig and dog (3 microgram per g), but peaks in the distal duodenum of guinea pig (1 microgram per g), no secretin being detectable in the ileum of these species. Secretin is relatively constant throughout the small intestine of the rat and rabbit (0.4 to 0.1 microgram per g). Sephadex gel filtration patterns of all species and throughout the gastrointestinal mucosa revealed primarily a single peak with elution characteristics identical with that of purified or synthetic porcine secretin. The "big" secretin prominent in Boots secretin may be an alteration product perhaps attributable to chemicals used to stabilize the preparation. The "intermediate secretin" described by others has not been detected. It is concluded that in a variety of mammalian species most of the immunoreactive secretin extractable from the intestinal tract lies distal to the proximal duodenum and is not distinguishable from duodenal secretin in terms of molecular size.

Animals↗
PubMed1978

Plasma secretin concentrations in fasting and postprandial state in man.

Plasma immunoreactive secretin concentrations were determined in both healthy subjects and patients with duodenal ulcer. The modified radioimmunoassay method could detect significant increases in the plasma secretin concentrations when 0.05 N HCl was infused intraduodenally at a rate of 1.1 and 2.2 ml/min. The mean fasting plasma secretin concentration of 13 normal healthy subjects was 4.4 +/- 0.38 pg/ml which was significantly less (P less than 0.01) than that of 13 duodenal ulcer patients, 6.9 +/- 0.64 pg/ml. In both groups ingestion of a meat-containing meal resulted in significant increase in the plasma secretin concentrations. Recording of pH from proximal duodenum indicated that pH fell periodically below 4.5 during the postprandial period, indicating that only a short segment of proximal duodenum was exposed to acid after meal. The postprandial rise in plasma secretin levels was abolished when antral pH was raised 5.5 by intragastric infusion of 0.3 N NaHCO3 solution. These observations indicate that although fasting plasma secretin levels are low, the plasma secretin levels increase significantly after ingestion of a meal. This increase appears to be attributable to an increased amount of acid delivered to the proximal duodenum, and patients with duodenal ulcer were found to release more secretin during the postprandial period than normal subjects.

Adult↗
PubMed1978

Secretion pattern of secretin in man: regulation by gastric acid.

Median concentration of plasma secretin in the fasting state in 11 achlorhydria patients, 17 normal subjects, eight duodenal ulcer patients, and 11 Zollinger-Ellison patients was 0.3, 1.2, 2.5, and 5.9 pmol x 1(-1), respectively. Aspiration of gastric acid normal subjects and duodenal ulcer patients was followed by a significant lowering of the plasma secretin concentration. In normal subjects insulin-induced hypoglycaemia resulted in increased secretin levels when gastric acid was allowed to enter the duodenum, whereas no changes were observed when gastric acid was aspirated. Simultaneous measurements of intraduodenal pH and plasma secretin concentration in the fasting state and in response to a meal showed that rapid falls in intraduodenal pH were followed by short-lived increments in plasma secretin concentration. These changes in pH and in secretin levels were diminished after cimetidine. It is concluded that gastric acid in man does trigger release of secretin and that secretin is secreted intermittently both in the fasting state and in response to a meal when boluses of acid enter the duodenum.

Adult↗
PubMed1977

Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH.

The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli.

Animals↗
PubMed1979

Effect of CCK-octapeptide and secretin on amylase secretion in isolated rat pancreatic acinar cells.

Isolated acinar cells from rat pancreas responded well to hormonal treatment. Both secretin (synthetic and highly purified from porcine origin) and CCK-octapeptide stimulated amylase secretion in these cells. The response in both cases was very rapid. A maximal output of enzyme was reached within 5-10 min after the addition of hormones. The concentration producing maximal output for synthetic secretin (Schwarz/Mann) was 5 x 10(-8) M, synthetic secretin (Squibb), 10(-5) M, for purified porcine secretin, 10(-5) M, and for CCK-octapeptide was 5 x 10(-10) M. Secretin (2-fold at optimal concentration) was found to be less efficient compared to CCK-octapeptide (5-fold at optimal concentration) in stimulating amylase release. A combination of secretin and CCK-octapeptide had a synergistic action in stimulating enzyme release by the acinar cells. In addition, pretreatment of acinar cells with secretin potentiated the secretory response of the treated cells to CCK-octapeptide. To a lesser extent pretreatment with CCK-octapeptide also increased the effect of secretin in stimulating enzyme secretion.

Amylases↗