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PubMed1978

The effect of fat on secretin release.

The effect of graded doses of intravenously infused secretin and intestinally perfused sodium oleate and HCl on pancreatic exocrine secretion and plasma secretin was determined in cats and dogs prepared with pancreatic fistulas. The pancreatic dose--response curves for bicarbonate following duodenal perfusion of oleate and HCl in cats were almost identical and paralleled the response to exogenous secretin. Although the bicarbonate response to oleate in dogs was less pronounced than the response to HCl or secretin, the bicarbonate output was observed to increase relative to protein output with increasing doses of the intestinally perfused fat. These observations suggested that secretin or a substance with secretin-like activity may be released from the intestine on contact with fat. The inability to detect changes in secretin immunoreactivity in both cats and dogs with increasing doses of oleate suggests that if secretin is released, it is in amounts undetectable by our radioimmunoassay or that some other unknown substance with secretin-like activity may be released.

Animals↗
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↗
PubMed1976

[Redioimmunoassay for secretin (author's transl)].

The synthesis of a secretin with an elongated N-terminus, namely Nalpha-(deaminotyrosyl-beta-alanyl)- secretin (DATA-secretin), using a conventional strategy, is described. After purification of the product by means of ion exchange chromatography on SP-Sephadex C-25 and by continuous carrier-free electrophoresis, immunological studies on the synthetic DATA-secretin were carried out using secretin antibodies. In comparison to 125iodine-labelled secretin and [Tyr6]secretin, 125iodine-DATA-secretin proved to be by far the best "tracer". Elaboration of a radioimmunoassay for secretin is therefore possible.

Animals↗
PubMed1978

Effect of secretin on basal- and glucose-stimulated insulin secretion in man.

Plasma immunoreactive secretin and insulin concentrations were measured in fasting normal humans after intraduodenal infusions of hydrochloric acid, isotonic or hypertonic glucose. The effect of intraduodenal acidification or intravenous bolus injections of secretin on plasma insulin concentrations during infusions of glucose was also examined. The intraduodenal glucose load did not cause an increase in plasma secretin concentrations. Secretin concentrations rose after acid both in the fasting state and during infusions of glucose. A concomitant rise in insulin levels was however only observed during infusions of glucose. Intravenous injection of secretin in a dose which mimicked the response to intraduodenal acidification was without effect on the glucose-stimulated insulin release, while a 30 times higher dose caused a highly significant augmentation of the insulin release. The insulin response pattern to this high dose of secretin differed completely from that observed after intraduodenal infusion of acid. It is concluded and confirmed that the stimulating effect of secretin on insulin secretion is pharmacological and that secretin plays no significant role in the entero-insular axis.

Adult↗
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↗
PubMed1976

Radioimmunoassay of secretin in plasma.

A sensitive, specific and reproducible radioimmunoassay for secretin is described. Antibodies were readily produced against low microgram quantities of synthetic secretin. The secretin antibodies did not cross-react with the structurally similar G.I.P., V.I.P., or glucagon. Synthetic secretin was iodinated using Chloramine "T" and purified by a two-state procedure incorporating gel filtration and radient elution from a cation exchange column. Plasma samples were found to produce variable interference in the assay necessitating the incorporation of secretin-free "blands" for each patient's plasma. Production of secretin-free plasma was by incubation of plasma samples at 37 degrees C for 96 hours. The sensitivity of the assay was 12.5-25 pg/ml. Normal fasting secretin levels were 21 +/- S.E. 7 pg/ml. A mean rise in plasma secretin to 220 pg/ml was observed after intraduodenal acidification.

Animals↗
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↗
PubMed1978

Effect of secretin on plasma insulin and glucagon in man.

To investigate the effect of physiological doses of secretin on pancreatic A and B cell functions, secretin was infused at a rate of 0.5, 1.0 and 2.0 clinical unit per kg body weight per hr into eight normal men for 30 min or 60 min after an over-night fast, and changes in plasma immunoreactive insulin (IRI) and glucagon immunoreactivity (GI) were measured while monitoring circulating secretin levels by a radioimmunoassay. During the infusion of secretin, the plasma immunoreactive secretin (IRS) levels rose to 140-390 pg/ml which was within a range of the physiological fluctuation in plasma secretin levels reported hitherto. No significant alteration of plasma IRI and GI levels could be demonstrated during these simulated physiologic infusions of secretin. These data suggest that, in humans, the physiological dose of secretin does not influence insulin and glucagon secretion from the pancreas in the basal state.

Adult↗
PubMed1979

The effect of duodenal acidification on plasma secretin and gastrin and pancreatic bicarbonate secretion in man.

Plasma secretin, plasma gastrin and pancreatic bicarbonate output were measured in three healthy youths before and after a 10 min period of duodenal infusion of 50, 75 and 100 ml 100 mmol/1 HCl. Plasma secretin rose to a shortlived peak within 10 min, whereas plasma gastrin fell gradually to values significantly below the basal level 60 min after the start of duodenal acidification. Pancreatic bicarbonate output showed a more sustained increase following duodenal acidification. Significant positive correlations were obtained between plasma secretin and infused dose of HCl, between pancreatic bicarbonate output and infused dose of HCl and between plasma secretin and pancreatic bicarbonate output. The calculated maximal pancreatic bicarbonate output (Vmax) of 30.6 mEq/h and the calculated dose of secretin to elicit half maximal pancreatic bicarbonate output (S50) of 0.2 CU/kg-h following duodenal acidification were comparable to that seen after intravenous infusion of secretin. No significant correlation was found between plasma secretin and plasma gastrin. It is suggested that the pancreatic stimulation subsequent to duodenal acidification is mainly effected by release of secretin, and that the fall in plasma gastrin may be caused by a HCl-induced inhibition of gastrin release from the duodenum.

Adult↗
PubMed1978

Radioimmunoassay of secretin in acidified plasma.

Antibody was readily produced in a rabbit against synthetic porcine secretin coupled to BSA. The final dilution of the antiserum to bind 50% of 1 fmol 125I-labeled secretin was 1 : 150,000. The effective equilibrium constant (Keff) according to Scatchard was 3.4 X 10(11) l/mol, the average equilibrium constant (Ko) according to Sips 3.5 X 10(11) l/mol, and the index of heterogeneity (alpha) according to Sips 1,00. No cross reactivity was found for gastrin, glucagon and insulin. 125I-labeled synthetic porcine secretin was prepared by the Chloramine-T-method, and the label purified on a Sephadex G-15 column followed by a SP Sephadex C-25 column had a specific radioactivity of 1.150 muCi/nmol. The radioimmunoassay method described has a detection limit of 1.6 pmol/l with 95% confidence limit, a within assay precision of 9,6%, and a between assay precision of 12.8%. It allows detection of fasting plasma secretin in the low pmol/l range, and the rather sharp rise and fall in plasma secretin subsequent to a brief period of duodenal acidification. The problem involved in measuring plasma secretin have been overcome by acidification of the plasma, and by subtracting the "apparent" secretin concentration in corresponding secretin-free plasma prepared by incubation at 37 degrees C for 96 h for each subject.

Animals↗
PubMed1976

Production and evaluation of antibodies for radioimmunoassay of secretin.

In order to produce antibodies for radioimmunochemical analysis of secretin in plasma, 16 rabbits were immunized; two different immunization schemes were followed. All rabbits produced detectable antibodies to secretin. The final dilution of the antisera necessary to bind 50% of 5 fmol [125I]secretin varied from 1:5,000 to 1:2,300,000. The avidity of antisera, expressed by the equilibrium constant, ranged from 5 x 10(6) 1 x mol-1 to 3 x 10(11) 1 x mol-1. Six rabbits produced antisera that displayed avidity sufficient for measurement of the physiologic concentrations of secretin in plasma (Keff greater than 10(11) 1 x mol-1). The equation of Sips was used to evaluate the heterogeneity of the antibodies. Seven of the 16 antibodies to secretin had a heterogeneity index of 0.90 or more. Cross-reactivity with structurally related peptide hormones (glucagon, vasoactive intestinal peptide, gastric inhibitory peptide) was found to be negligible for the six antisera examined (those with the highest avidity). Three of the high-avidity antisera were examined for reactivity with secretin fragments. They all bound the C-terminal secretin tricosa and tetradecapeptides almost as well as pure natural secretin, whereas the reactivity with the N-terminal tetradecapeptide was slightly lower.

Animals↗
PubMed1976

Diagnosis of gastrinoma by the secretin suppression test.

In contrast to normal physiologic feedback suppression of serum gastrin by secretin, a paradoxic rise in the serum gastrin level has been observed in patients with gastrinoma after the administration of exogenous secretin. Exploitation of this phenomenon in the differential diagnosis of gastrinoma has been restricted by limited individual experience. Serial serum specimens for gastrin radioimmunoassay were collected from 13 patients with histologically proved gastrinoma both before and after the administration of Boot's secretin, 3 units per kilogram. Thirty-nine others with histologically proved gastrinoma who had been studied with exogenous secretin were identified in the literature. Both the peak gastrin and the integrated gastrin responses were increased after secretin administration in each of the patients in this combined series, although the magnitude of the increase was small in four patients. The absence of physiologic suppression by secretin implies neoplastic autonomy of gastrin releasing sites. While an augmented gastrin response to secretin is commonly seen in patients with gastrinoma, from a physiologic standpoint, a lack of suppression constitutes a positive secretin suppression test. Accumulated experience is consistent and suggests that this test is an important adjunt in the differential diagnosis of hypergastrinemia.

Gastrins↗
PubMed1977

Distribution, ontogeny and ultrastructure of the mammalian secretin cell.

Immunocytochemically, secretin cells have been demonstrated to occur in the duodenum and jejunum of several mammals. Calculations on the relative frequency of such cells indicate that the bulk of secretin occurs in the jejunum, a fact supporting the view that secretin may be released by physiological stimulants other than hydrochloric acid. Electron microscopical identification of cat and pig secretin cells confirmed their identity with the ultrastructurally defined S cells, and staining experiments revealed that secretin cells were argyrophilic both with the method of Grimelius and with that of Hellerström and Hellman. Secretin cells are detected already in the 17-day old fetal rat duodenum and show a developmental pattern similar to that displayed by the gastrin cells. It is suggested that secretin may play a role in the early regulation of growth of the fetal gastrointestinal tract.

Animals↗
PubMed1978

Secretin secretion in patients with duodenal ulcer, chronic pancreatitis and diabetes mellitus.

Secretin releasing response to intraduodenal acid infusion was investigated in 15 cases of diseased control, 7 cases of duodenal ulcer, 5 cases of chronic pancreatitis, and 6 cases of diabetes mellitus. Plasma secretin levels in response to duodenal acidification were less in duodenal ulcer and the appearance of the maximal peak was delayed compared with that found in control. It is suggested that the secretin release was impaired in duodenal ulcer in spite of hypersecretion of gastric acids. In chronic pancreatitis, secretin releasing response to acidification was markedly impaired, in addition, inhibition of secretin release by bicarbonate was diminished due to a lack of bicarbonate flow from the pancreas. On the other hand, although the response of secretin release in diabetes mellitus was also lower compared with that in control group, the capacity of secretin response showed values in-between control subjects and chronic pancreatitis. This research was supported in part by grant from the Ministry of Education, Science and Culture in Japan.

Adolescent↗
PubMedDate not supplied

Effect of secretin on pacemaker activity and contractility in the isolated blood-perfused atrium of the dog.

1. The effects of secretin on inotropic and chronotropic activity were investigated in nine isolated canine atrium preparations which were suspended in a bath and perfused with arterial blood from a carotid artery of a heparinized donor dog. 2. Secretin administered into the cannulated sinus node artery in a dose range of 0-1-10 units produced a dose-related positive inotropic and a biphasic chronotropic effect. 3. The positive chronotropic and inotropic responses to secretin were not suppressed by treatment with alprenolol in doses which blocked responses to noradrenaline. 4. The negative chronotropic response to secretin was not blocked by atropine in doses which blocked the response to acetylcholine. 5. After treatment with glucagon, secretin produced dose-related negative chronotropic and a positive inotropic effects. Thus glucagon may antagonize the positive chronotropic effect of secretin. 6. From these results, it is concluded that secretin has a direct effect on atrial rate and contractility.

Alprenolol↗
PubMed1978

Secretory effects of secretin on isolated perfused porcine pancreas.

The effect of pure natural porcine secretin on endocrine and exocrine pancreatic secretion was studied in the totally isolated perfused porcine pancreas. The exocrine pancreatic responses to secretin correspond well with those obtained in the anesthetized pig. The lowest concentration of secretin observed to increase pancreatic secretion was 2.8 pmol/liter, whereas the maximum pancreatic responses were obtained at a secretin concentration of 92 pmol/liter. The infusion of secretin in concentrations ranging from 2.8 to 278 pmol/liter in the presence of a constant concentration of glucose (7.5, 5.0, or 3.5 mmol/liter) was without effect on the insulin and glucagon release. Infusion of secretin at a concentration of 834 pmol/liter in the presence of glucose at 7.5 mmol/liter provoked a significant (P less than 0.01) short-lived increase in insulin secretion. However, there was no effect on the glucagon secretion. The results of this study indicate that neither the augmented insulin response nor the suppression of glucagon elicited by oral glucose depend on secretin.

Animals↗