Plasma Secretin Concentration Research Articles

1215-P: Effects of Exogenous Secretin on Postprandial Plasma Glucose and Lipids and Gallbladder Motility and Hemodynamics in Man

Secretin is best known for its effect on pancreatic exocrine secretion. It also has osmoregulatory effects and was recently identified as a potential target for the treatment of obesity. We investigated the effects of a 5-hour intravenous (iv) secretin infusion on postprandial plasma glucose and lipids and gallbladder motility as well as hemodynamics in healthy males. In a randomized, double-blind, placebo-controlled, crossover study, 25 healthy males (25.7 ± 6.1 (mean ± SD) years; BMI 23.4 ± 1.8 kg/m2) underwent two 5-hour iv infusions of secretin (1 pmol/kg/min) or placebo (saline), with an interposed 8-week washout period. After 30 minutes of infusion, a standardized liquid mixed meal was ingested. Prior to and with regular intervals during the 5-hour infusions, blood samples were drawn, ultrasonography of the gallbladder performed, and hemodynamics measured. Steady-state plasma concentrations of secretin amounted to 113 ± 2 pmol/L, i.e., ~20-fold higher than physiological levels. Postprandial plasma triglyceride excursions were higher during secretin than placebo infusions (baseline-subtracted area under curve: 111 ± 49 vs. 83 ± 36 min × pmol/L [P = 0.012]), whereas excursions in glucose, glycerol and free fatty acids were similar during placebo and secretin infusions. Compared to placebo, secretin reduced maximum gallbladder ejection fraction by 32 ± 27% (P <0.001) and increased mean systolic and diastolic blood pressure by 5.3 ± 4.5 (P <0.039) and 2.2 ± 3.2 mmHg (P <0.001), respectively, and increased heart rate by 5.5 ± 3.6 bpm (P <0.001). We conclude that a 5-hour iv infusion of secretin in healthy males has no effect on fasting and postprandial glucose levels, but reduces postprandial gallbladder contraction, while increasing plasma triglycerides, blood pressure and pulse. Disclosure M. J. Bentzen: None. S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. B. Hartmann: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. M. B. Christensen: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.

Effects of early enteral feeding on fecal elastase 1 and plasma secretin

Enteral feeding is known to be effective on the development of gut hormone secretion and pancreatic exocrine function. The aim of the present study was to examine the effects of extremely early enteral feedings on the development in very low-birthweight (VLBW) infants. Fecal elastase 1 and plasma secretin concentrations were measured at four different periods during the first 28 days of life in VLBW infants, with extremely early enteral feeding starting within 24 h of birth, as well as in control infants. Fecal concentrations of elastase 1 at 7, 14 and 28 days after birth were significantly higher than those at 1 or 2 days in both the early feeding and control groups. Fecal elastase 1 levels in the early feeding group were significantly higher than those in the control group at 7 and 14 days after birth. The plasma concentration of secretin at 14 days after birth was significantly higher than that at 1 or 2 days and 7 days after birth in the early feeding group. No significant differences in plasma secretin levels were detected between the early feeding and control groups at 1 or 2 days, 7 days and 28 days after birth, but a significant difference in secretin level was observed between the two groups at 14 days after birth. Extremely early enteral feedings may play an important role in the development of pancreatic exocrine function and secretin secretion in the early period of life in VLBW infants.

Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats.

5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and neurotransmitter regulating gastrointestinal functions. 5-HT receptors are widely distributed in gastrointestinal mucosa and the enteric nervous system. Duodenal acidification stimulates not only the release of both 5-HT and secretin but also pancreatic exocrine secretion. We investigated the effect of 5-HT receptor antagonists on the release of secretin and pancreatic secretion of water and bicarbonate induced by duodenal acidification in anesthetized rats. Both the 5-HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron at 1-100 microg/kg dose-dependently inhibited acid-induced increases in plasma secretin concentration and pancreatic exocrine secretion. Neither the 5-HT(1) receptor antagonists pindolol and 5-HTP-DP nor the 5-HT(4) receptor antagonist SDZ-205,557 affected acid-evoked release of secretin or pancreatic secretion. None of the 5-HT receptor antagonists affected basal pancreatic secretion or plasma secretin concentration. Ketanserin or ondansetron at 10 microg/kg or a combination of both suppressed the pancreatic secretion in response to intravenous secretin at 2.5 and 5 pmol x kg(-1) x h(-1) by 55-75%, but not at 10 pmol x kg(-1) x h(-1). Atropine (50 microg/kg) significantly attenuated the inhibitory effect of ketanserin on pancreatic secretion but not on the release of secretin. These observations suggest that 5-HT(2) and 5-HT(3) receptors mediate duodenal acidification-induced release of secretin and pancreatic secretion of fluid and bicarbonate. Also, regulation of pancreatic exocrine secretion through 5-HT(2) receptors may involve a cholinergic pathway in the rat.

A secretin releasing peptide exists in dog pancreatic juice

Canine pancreatic juice has been shown to stimulate exocrine pancreatic secretion in the dog. In the present study we investigated whether there is a secretin-releasing peptide in canine pancreatic juice. Pancreatic juice was collected from the dogs with Thomas gastric and duodenal cannulas while pancreatic secretion was stimulated by intravenous administration of secretin at 0.5 μ/gk/gh and CCK-8 at 0.2 μg/kg/h, respectively. The pancreatic juice was separated into three different molecular weight (MW) fractions (Fr) by ultrafiltration (Fr 1; MW > 10,000, Fr 2; MW = 10,000 − 4,000 and Fr 3; MW < 4,000), respectively. All the fractions were bioassayed in anesthetized rats. Fraction 3 dose-dependently and significantly stimulated pancreatic juice flow volume from 78.0% to 99.4% (p < 0.05) and bicarbonate output from 128.9% to 202.1% (p < 0.01), respectively. Plasma secretin concentration also increased from 1.2 ± 0.5 pM to 5.0 ± 0.8 pM and 6.0 ± 1.0 pM (p < 0.05). None of these fractions increased pancreatic protein secretion or plasma CCK level. The stimulatory effect of Fraction 3 on pancreatic secretion and the release of secretin was completely abolished by treatment with trypsin (1 mg ml for 60 min at 37 ° C) but not by heating (100 ° C, 10 min). Intravenous injection of a rabbit anti-secretin serum, which rendered plasma secretin almost undetectable in rat plasma, also abolished Fr 3-stimulated pancreatic secretion of fluid and bicarbonate secretion. These observations suggest that a secretin-releasing peptide exists in the canine pancreatic juice. It is trypsin-sensitive and heat-resistant. This peptide may play a significant physiological role on the release of secretin and regulation of exocrine pancreatic secretion.

Fish Oil Reduces Gastric Acid Secretion

The aim of the present investigation was to study gastric acid secretion and release of gastrin, cholecystokinin (CCK), and secretin during intraduodenal perfusion of either fish oil or trioleate. Seven healthy volunteers were stimulated on two separate days in random order with intraduodenal perfusates of either fish oil or trioleate. Intravenous infusion with gastrin-17 was used as a background stimulation in doses mimicking a postprandial situation (39.9 +/- 4.8 pmol/l fish oil and 43.6 +/- 3.8 pmol/l trioleate). Gastric acid secretion increased significantly from a basal level of 0.7 +/- 0.1 meq/15 min to 4.0 +/- 0.6 meq/15 min (P < 0.05) before perfusion of fish oil, which reduced gastric acid secretion to 1.9 +/- 0.4 meq/15 min (P < 0.01). After termination of fish oil perfusion gastric acid secretion increased to preperfusion concentrations (P < 0.01). Perfusion of trioleate did not influence gastric acid secretion. Plasma concentrations of CCK rose significantly during perfusion of fish oil (from 2.8 +/- 0.6 pmol/l to 4.4 +/- 0.7pmol/l, P<0.01), whereas trioleate only tended to increase CCK concentrations. Plasma concentrations of secretin did not change during perfusion of fish oil; however, concentrations were significantly lower during and after perfusion of trioleate (P < 0.01). The present study shows that intraduodenal perfusion of fish oil is associated with a significant reduction of the gastric acid secretion stimulated by gastrin in healthy humans.

Secretin and Gastric Lipase Secretion

Background: Gastric lipase secretion is stimulated by gastrin in plasma, but its regulation by secretin is unknown. Methods: In 7 normal persons we investigated the effect of exogenous secretin on the output of gastric lipase stimulated by intravenous gastrin-17. The gastric content was measured using a nasogastric tube for aspiration. The quantitative lipase secretion was measured by an enzyme-linked immunosorbant assay (ELISA) and the lipolytic activity by a kinetic assay. Plasma concentrations of secretin and gastrin were measured by radioimmunoassay. Results: Gastric lipase secretion (the quantity as well as the lipolytic activity) was significantly stimulated by gastrin. In response to secretin infusion, the lipolytic activity increased as acid secretion decreased. Conclusion: Secretin in postprandial concentrations does not influence the quantitative gastric lipase secretion stimulated by gastrin, but it increases lipolytic activity due to inhibition of acid secretion.

Regulation of porcine biliary secretion by secretin.

The importance of physiological plasma levels of secretin in biliary bicarbonate secretion is not known. However, in anaesthetized pigs the substantial hepatic output of bicarbonate into the duodenum in response to low doses of secretin exceeds pancreatic bicarbonate output. The aim was therefore to study the relationship between duodenal acidification, secretin and hepatic biliary bicarbonate output in the conscious pig. Göttingen minipigs (n = 22) were cholecystectomized and the common bile duct catheterized. The biliary bicarbonate secretion in response to intraduodenal HCl, secretin or pentagastrin given intravenously, and to meal was studied. Intraduodenal HCl infusion, secretin and pentagastrin given intravenously augmented hepatic bicarbonate output and plasma secretin concentrations significantly. The secretin response to acidification was sufficient to explain the subsequent increase in biliary bicarbonate secretion. Hepatic bicarbonate secretion and concentrations of CCK and secretin in plasma increased postprandially. Exclusion of bile salts from the duodenum abolished postprandial increase in bile volume and increased release of CCK in fasting and fed pigs whereas secretin release was diminished. The results demonstrate that hepatic bicarbonate secretion is stimulated by endogenous secretin and therefore may have a physiological role in duodenal neutralization.

Comparison of the Kinetics of Pancreatic Secretion and Gut Regulatory Peptides in the Plasma of Preruminant Calves Fed Milk or Soybean Protein

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.

Gastric lipase secretion after sham feeding and cholinergic blockade.

Our purpose was to examine gastric lipase secretion after cephalic stimulation (sham feeding) and to examine the effect of cholinergic blockade. Eight healthy volunteers, four women and four men, age 21-58 years, were studied twice on separate days. They were sham fed with and without infusion of atropine. Gastric content was measured and the amount as well as the activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin (CCK) were measured simultaneously by radioimmunoassays. Cephalic stimuli can evoke human gastric lipase secretion, and this effect was almost ablated by atropine blockade of cholinergic receptors. The concentrations of CCK and secretin in plasma were unaffected by sham feeding with or without atropine blockade, whereas gastrin was stimulated by sham feeding after atropine blockade. Gastric lipase secretion in man is apparently controlled by interacting vagal and hormonal mechanisms.

Importance of vagus nerves in duodenal acid neutralization in anesthetized pigs.

During the cephalic phase of gastric acid secretion, vagally mediated synchronous stimulation of bicarbonate provides protection against the acid. The purpose of this study was to determine simultaneously the effect of electrical vagal stimulation (EVS) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion, thereby estimating their relative importance in vagally induced duodenal acid neutralization. Splanchnicotomy increased vagally induced pancreaticobiliary bicarbonate secretion, whereas duodenal mucosal bicarbonate secretion was unchanged. After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz) significantly increased pancreatic bicarbonate secretion (0-4.17 mmol/h), hepatic bicarbonate secretion (0.16 to 0.22 mmol/h), and duodenal mucosal bicarbonate secretion (0.17 to 0.31 mmol/h). Pancreaticobiliary bicarbonate secretion was atropine resistant, whereas vagally induced duodenal mucosal bicarbonate secretion was diminished by atropine (2.0 mg/kg). After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz) had no effect on portal plasma concentration of secretin, whereas vasoactive intestinal peptide was increased (14-29 pM). EVS at 12 Hz with varying duration (3 or 10 ms) and amplitude (3-50 mA) had no further effect on the bicarbonate secretion from the three organs. In addition, biliary [14C]mannitol clearance was shown not to be a reliable marker of canalicular bile secretion in pigs. These results suggest that in the anesthetized pig 1) vagal stimulation is only of minor importance to hepatic bicarbonate secretion; 2) vagal stimulation activates pancreatic bicarbonate secretion through both cholinergic muscarinic and noncholinergic transmission; and 3) vagal stimulation induces duodenal mucosal bicarbonate secretion mainly through cholinergic muscarinic transmission. In conclusion, these results suggest that only pancreatic and duodenal bicarbonate production play a role in vagally induced duodenal acid neutralization.

Neuronal regulation of the release and action of secretin-releasing peptide and secretin

The acid-stimulated release of secretin is mediated by a secretin-releasing peptide (SRP) in rats. In the present study we investigated to determine whether a neural mechanism(s) is involved in the regulation of release and action of SRP in anesthetized rats. A concentrated acid perfusate (CAP) containing SRP was obtained from donor rats. CAP administered to recipient rats significantly increased pancreatic flow volume (81.6 +/- 18.3%), bicarbonate output (188.7 +/- 15.6%), and plasma secretin level (from 0.9 +/- 0.2 to 4.4 +/- 0.5 pM). However, this effect was attenuated by CAP from donor rats pretreated with tetrodotoxin (TTX), propranolol, bilateral subdiaphragmatic vagotomy (BSV), or systemic and topical administration of capsaicin. In contrast, CAP from donor rats pretreated with phentolamine, atropine, or hexamethonium did not alter the increase in plasma secretin concentration and pancreatic secretion. Moreover, the action of CAP on secretin release was significantly inhibited in the recipient rats pretreated with TTX, BSV, and topical applications of capsaicin but was not suppressed in the recipient rats pretreated with atropine, hexamethonium, or propranolol. Furthermore, perivagal and duodenojejunal mucosal application of capsaicin abolished the pancreatic secretory response to secretin at 5 pmol.kg-1.h-1. In conclusion, the release and action of both SRP and secretin are mediated by a vagal afferent pathway. beta-Adrenergic receptors also play a significant role in the release of SRP.

Preparation of specific antiserum of secretin and its use in time-resolved fluoroimmunoassay

We have prepared a specific anti-secretin antiserum and developed a sensitive time-relevant fluoroimmunoassay (TR-FIA) for secretin. An anti-secretin antiserum was produced in rabbit by immunization with synthetic secretin C-terminal 8 residue conjugate to chicken serum albumin as antigen. The TR-FIA was based on the competition between free secretin and biotinylated secretin as a tracer for rabbit anti-secretin antibodies on a goat anti-rabbit IgG antibody coated microtiter plate. After separation of bound and free fractions, a solution of europium (III) ion chelate labeled streptavidin (Eu-SA) was added to the biotinylated secretin bound on the microtiter plate. The microtiter plate was washed and then Eu-SA activity was measured by time-resolved fluorometry. In this TR-FIA, the measurable range of secretin was from 2.5 to 100 pg/assay and the specificity was less than 0.01% against other peptide hormones. For the measurement of secretin in the human plasma, a sample was required for the pretreatment in order to separate from interfering substances. The mean recovery of secretin using commercially reverse phase column was 80.2% (n = 11). The plasma secretin concentrations of normal subjects and those with various diseases could be measured by this proposed TR-FIA.

Effect of protein derivatives on pancreatic secretion and release of secretin and CCK in rats.

We investigated the effect of intraduodenal administration of oligopeptide and a mixed amino acid solution, which contains the same amino acid composition as oligopeptide, on pancreatic exocrine secretion and the release of secretin and cholecystokinin (CCK). Anesthetized rats were prepared with pyloric ligation and cannulation of pancreatic duct and bile duct. Protein derivatives in three different doses (oligopeptide: 25, 100, and 400 mg/h; and mixed amino acid solution: 70, 140, and 280 mg/h, pH 7.0) were infused into the duodenum for 1 h. Pancreatic juice was collected, and plasma concentrations of secretin and CCK were measured by radioimmunoassay. In addition, the effect of intravenous injection of an antisecretin serum or a CCK antagonist, loxiglumide, on pancreatic secretion stimulated by oligopeptide or mixed amino acid solution was also studied. Oligopeptide produced a significant dose-related increase in pancreatic secretion including volume, HCO3-, amylase, and trypsin output, plasma secretin (r = 0.792, P < 0.001), and plasma CCK (r = 0.421, P < 0.01). Similarly, mixed amino acid solution produced a dose-related increase in pancreatic juice volume, HCO3-, amylase, and trypsin output. Compared with CCK, the percentage increase in plasma secretin was 7.3x and 2.8x higher in response to oligopeptide (400 mg/h) and mixed amino acid solution (280 mg/h), respectively. An antisecretin serum almost completely inhibited volume flow and HCO3- output stimulated by oligopeptide as well as mixed amino acid solution, but not amylase and trypsin output. In contrast, loxiglumide significantly suppressed amylase and trypsin output stimulated by protein derivatives, but did not affect volume flow or HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)

Local versus peripheral blood administration of cholecystokinin-8 and secretin on pancreatic secretion in calves.

The effects of local and peripheral administration of cholecystokinin-8 (CCK-8) and secretin on the interdigestive pancreatic secretion were examined in conscious preruminating calves. Six calves were surgically fitted with a pancreatic catheter and duodenal cannula, duodenal electrodes and strain gauges, and cooling devices on the cervical vagi. Local intra-arterial (I.A.) infusions were made into the duodenal branch of the right gastroepiploic artery, and peripheral infusions (I.V.) into the external jugular vein. CCK-8 and secretin were infused I.A. and I.V. for 5 min (0, 10, 30 and 100 pmol (kg body weight)-1) during the asecretory phase of the pancreatic interdigestive cycle. CCK-8 and secretin at 100 pmol kg-1 were administered concomitant with reversible cold vagal blockade. Local infusion of CCK-8 without vagal blockade resulted in a significantly faster and stronger pancreatic response than the respective peripheral infusion, although CCK in peripheral blood plasma was paradoxically only minimally increased after I.A. CCK-8 in comparison with a marked increase after I.V. CCK-8. Vagal blockade noticeably decreased the pancreatic response for I.A. CCK-8, but not for I.V. CCK-8. Secretin produced similar pancreatic responses after I.V. and I.A. administration, but the plasma secretin concentration in peripheral blood was markedly lower after I.A. than after I.V. infusions. Cold vagal blockade uniformly reduced the stimulatory effect of I.A. and I.V. secretin infusion on the exocrine pancreas. In calves, CCK-8 apparently stimulates the exocrine pancreas by two different mechanisms: by a direct effect that is vagally independent as well as by an indirect effect in the duodenum that is vagally dependent. The indirect effect of secretin in the duodenum is less clear, but both direct and indirect effects of secretin depend on vagal integrity.

Secretin as a Potential Mediator of Antiulcer Actions of Mucosal Protective Agents

Recently, we have reported that several nonacid agents including phenylpentol, methanol extract of licorice root (FM 100), plaunotol, and teprenon stimulate release of endogenous secretin in humans, dogs, and rats. The latter three are antiulcer agents developed in Japan that have a protective effect on the gastric mucosa. We have clearly shown that plaunotol inhibits postprandial gastrin release and gastric acid secretion that parallel the increase in plasma secretin concentration. It has also been recently demonstrated that the secretin-induced inhibition of gastric acid secretion in rats is completely blocked by indomethacin, a potent inhibitor of prostaglandin synthesis. It appears that the inhibitory action of secretin on gastric acid secretion is mediated mainly by endogenous prostaglandins. Because the three antiulcer agents FM 100, plaunotol, and teprenon have been shown to increase the content of endogenous prostaglandins in the gastric mucosa, endogenous secretin released by these agents may play a significant role in their mucosal protective action. It is concluded that the antiulcer effect of these drugs could in part be attributable to their unique ability to release endogenous secretin, and that secretin is a potential mediator of the antiulcer actions of mucosal protective agents.

Characterization of secretin release in response to food and intraduodenal administration of fat and hydrochloric acid

The development and validation of a radioimmunoassay that detects release of secretin in plasma in response to low doses of secretagogues [intraduodenal HCl (0.033 meq/min); intraduodenal sodium oleate (0.04 mmol/min)] or an oral mixed meal in conscious dogs is described. Plasma secretin levels increased significantly (P less than 0.05) in response to an oral mixed meal in conscious dogs from a basal level of 4.0 to a peak level of 12.3 pg/ml at 15 min. Infusion of graded doses of HCl (2, 4, 8, 16, meq/hr for 30 min) intraduodenally in six dogs resulted in significant elevation of plasma secretin levels in a dose-dependent manner. The pancreatic bicarbonate and volume outputs correlated with the dosage of HCl administered and with the elevations in plasma secretin concentrations. Intraduodenal infusion of increasing doses of sodium oleate (2.4, 4.8, 9.6, and 19.2 mmol in 15-min periods) resulted in a significant (P less than 0.05) elevation of plasma levels of secretin.

Somatostatin Analog, SMS 201-995, Inhibits Pancreatic Exocrine Secretion and Release of Secretin and Cholecystokinin in Rats

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.

Effects of MCI-727, a New Anti-Ulcer Agent, on Plasma Secretin Concentration in Rats and Dogs and Pancreatic Exocrine Secretion in Rats.

In the present study, we investigated the effects of MCI-727, a new anti-ulcer agent, on plasma immunoreactive secretin concentration in rats and dogs using secretin specific RIA with the ethanol extraction method. Plasma secretin levels were increased dose-dependently 10 min after oral administration of MCI-727 in rats (control: 5.5 +/- 0.6; MCI-727, 10 mg/kg: 10.4 +/- 2.6; 30 mg/kg: 15.3 +/- 1.5; 100 mg/kg: 20.7 +/- 2.6 pg/ml, n = 6). Teprenone also caused a significant increase of plasma secretin at 10 min after oral administration at the doses of 30, 100 and 300 mg/kg. Under the same conditions, MCI-727 and teprenone did not alter the plasma immunoreactive gastrin concentration in rats. From the results of the time course study, the increasing effect of MCI-727 (30 mg/kg, p.o.) on plasma secretin remained for at least 240 min after administration. On the other hand, the increasing effect of teprenone (200 mg/kg, p.o.) was only observed at 30 and 60 min after administration. Furthermore, MCI-727 had increasing effects on plasma secretin concentration in dogs, but teprenone had no effects in this species. The volume of pancreatic secretion and the pancreatic bicarbonate output increased after intra-duodenal administration of MCI-727 at 30 and 100 mg/kg in rats. Similar effects were also observed with teprenone (30-300 mg/kg, i.d.) or secretin (Secrepan, 0.1-1.0 unit/kg, i.v.).

Effects of MCI-727, a New Anti-Ulcer Agent, on Plasma Secretin Concentration in Rats and Dogs and Pancreatic Exocrine Secretion in Rats

Effects of MCI-727, a New Anti-Ulcer Agent, on Plasma Secretin Concentration in Rats and Dogs and Pancreatic Exocrine Secretion in Rats

Pancreatic, Hepatic, and Duodenal Mucosal Bicarbonate Secretion during Infusion of Secretin and Cholecystokinin: Evidence of the Importance of Hepatic Bicarbonate in the Neutralization of Acid in the Duodenum of Anaesthetized Pigs

The effect of infusion of secretin alone or in combination with cholecystokinin (CCK) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion was studied in anaesthetized pigs. After laparotomy, catheters were inserted into the common bile duct, the pancreatic duct, and both ends of the duodenum. Pancreatic, hepatic, and duodenal mucosal secretions were collected during intraportal infusion of increasing doses of secretin, either alone or in combination with CCK. During infusion of secretin in doses that caused physiologic increases in plasma secretin concentrations the liver produced significantly more bicarbonate than the pancreas. A physiologic dose of CCK augmented the effect of secretin on both hepatic and pancreatic bicarbonate secretion, but the hepatic production of bicarbonate was still larger than the pancreatic production. Neither secretin alone nor secretin combined with CCK caused any changes in duodenal mucosal bicarbonate secretion. These results suggest that the liver plays an important role in the neutralization of acid in the duodenum.