Plasma Secretin Concentration Research Articles

Hormonal mechanism of sodium oleate-stimulated pancreatic secretion in rats

We have investigated the role of two intestinal hormones, secretin and cholecystokinin (CCK), on the pancreatic exocrine secretion stimulated by sodium oleate in anesthetized rats. Each rat was prepared with a polyethylene tube in the proximal duodenum and ligation of the pylorus. To collect pancreatic juice, the common bile-pancreatic duct was cannulated near the duodenal wall while bile was diverted to the exterior. Intraduodenal infusion of sodium oleate at doses of 0.03, 0.06, 0.12, and 0.24 mmol/h resulted in significant increases in pancreatic secretion including fluid, bicarbonate, and protein output. The increases of the three parameters were dose dependent and were correlated well with the increases in plasma secretin and CCK concentrations. To further clarify their hormonal roles, we have repeated identical experiments under intravenous administration of a rabbit anti-secretin serum (0.1 ml) or CR 1409 (4 mg.kg-1.h-1), a CCK-receptor antagonist, or a combination of both the antiserum and CR 1409. The antiserum significantly suppressed volume flow and bicarbonate secretion with a minor inhibitory effect on protein secretion, whereas a normal rabbit serum did not. CR 1409 significantly suppressed all three parameters. The combined treatment with both the antiserum and CR 1409 almost completely abolished the pancreatic secretion. Atropine given intravenously significantly inhibited the protein output but did not influence volume flow or bicarbonate output in response to sodium oleate. We thus conclude that, in rats, fat-stimulated pancreatic secretion of volume flow and bicarbonate depends entirely on the circulating endogenous secretin and CCK but that the protein output appears to be under control of both hormonal and cholinergic controls.

Mechanism of acid-induced release of secretin in rats. Presence of a secretin-releasing peptide.

In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin. To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas. Donor rats were infused intraduodenally with 0.01 N HCl, 0.15 M NaCl, or a combination of 0.01 N HCl and 0.05 N NaHCO3 at 0.3 ml/min for 1.5 h, and the perfusates were collected via jejunal cannulas. The perfusates with pH adjusted to 6.0 were concentrated threefold and infused into the duodena of recipient rats. The concentrate of acid perfusate (CAP) significantly increased both pancreatic volume flow and bicarbonate output and plasma concentration of secretin, whereas concentrates of the saline perfusate (CSP) or the perfusate of a combination of 0.01 N HCl and 0.05 N NaHCO3 (CABP) did not influence pancreatic secretion or plasma concentration of secretin. The increased pancreatic secretion by CAP was attributed to increased circulating secretin because when secretin was immunoneutralized by a rabbit antisecretin serum, CAP-stimulated pancreatic secretion was abolished. The bioactivity of CAP was trypsin-sensitive and heat stable. The active substance in CAP had a molecular weight of less than 5,000 and greater than 1,000, as determined by ultrafiltration and bioassay. In conclusion, dilute HCl releases an S-RF into the upper small intestinal lumen to stimulate release of secretin. This substance, with molecular weight of less than 5,000, is heat stable and trypsin sensitive. Thus, the acid-stimulated release of secretin is mediated by a secretin-releasing peptide in the upper small intestinal lumen.

Effect of feeding on plasma secretin concentrations in sheep

Changes in plasma secretin concentration during the 24 hours after feeding were observed in five female sheep fed 1500 g of lucerne pellets and 300 g of orchard grass hay once daily. The pre-feeding concentration of plasma secretin was 50 +/- 9 pg ml-1. The plasma secretin concentration began to increase immediately after the beginning of feeding, reached values approximately double the pre-feeding values six hours after feeding, and remained significantly above the pre-feeding value for more than 10 hours after feeding (P less than 0.01 or less than 0.05).

Plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action in humans

Plaunotol, an acrylic diterpene alcohol, is a new antiulcer agent derived from the "plau-noi" plant and has been reported to stimulate the release of endogenous secretin in humans. We investigated the effect of plaunotol on postprandial gastrin release, comparing it to the effect of exogenous secretin in a physiological dose in eight healthy volunteers. Four sets of experiments were performed in each volunteer: (1) meal alone, (2) meal after intravenous ranitidine (50 mg), (3) meal after oral administration of plaunotol (320 mg) in addition to ranitidine, and (4) meal after ranitidine with simultaneous intravenous infusion of secretin (0.03 CU/kg/hr). The postprandial increase in plasma secretin concentration was significantly reduced by ranitidine, while postprandial gastrin release was markedly exaggerated. Plaunotol in combination with ranitidine significantly increased secretin release and inhibited gastrin release after a meal. Intravenous infusion of secretin resulted in significant suppression of postprandial gastrin release exaggerated by ranitidine. The present study indicates that plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action.

The effects of secretin on prolactin, estradiol, vasoactive intestinal polypeptide, and somatostatin levels in women

The effect of graded doses of intravenous secretin (0.5, 1.0, and 2.0 CU.kg-1.h-1) on serum prolactin and estradiol levels, as well as plasma vasoactive intestinal polypeptide and somatostatin levels was studied in 6 normally cycling and healthy women, and compared with the hormone levels obtained by a control infusion with physiologic saline (0.15 mol/l). A significant decrease in serum prolactin concentrations was found with increasing doses of secretin at steady-state levels of plasma secretin (+30 to +60 min). A significant negative correlation (p less than 0.007, r = -0.2764) existed between serum prolactin and plasma secretin concentrations at steady-state conditions. No effect of graded doses of secretin was observed on serum estradiol levels and plasma concentrations of vasoactive intestinal polypeptide and somatostatin. The results suggest a dose-related inhibitory effect of secretin on prolactin release in women.

Role of secretin and cholecystokinin in oleic acid-stimulated pancreatic secretion in rats

We investigated the possible role of endogenous secretin and cholecystokinin (CCK) on oleic acid-stimulated pancreatic exocrine secretion in anesthetized rats. Intraduodenal infusion of oleic acid (pH 6.5) in three different doses (0.06, 0.25 and 1 mmole/hr) resulted in dose-related increases in pancreatic juice volume, bicarbonate and amylase outputs (r = 0.665, 0.736 and 0.517, respectively) (P less than 0.001). Plasma secretin and CCK concentrations also elevated significantly in response to oleic acid, in a dose-related manner (r = 0.721 and 0.546, respectively) (P less than 0.001). There were statistically significant correlations between plasma secretin concentrations and bicarbonate outputs, and between plasma CCK concentrations and amylase outputs in response to oleic acid (P less than 0.01). Potent CCK antagonist, CR 1409 (5 mg/kg.hr) administered intravenously suppressed completely increase in amylase output induced by oleic acid, and partially in juice volume and bicarbonate output. It is concluded that both endogenous secretin and CCK play important roles on oleic acid-induced pancreatic secretion in rats.

Duodenal Disappearance Rate of Acid during Inhibition of Mucosal Bicarbonate Secretion

In order to investigate the relation between duodenal mucosal and pancreaticobiliary bicarbonate secretion, we have studied the effect of inhibition of mucosal bicarbonate secretion by indomethacin on the disappearance rate of acid and the concomitant plasma secretin concentrations. 10 healthy subjects were studied twice, with and without indomethacin pretreatment. By means of a double-lumen tube the duodenum was perfused with increasing amounts of acid (0, 3.0, 6.0 and 9.5 mmol/h) and the disappearance rate of acid, pH of duodenal aspirate and plasma secretin were measured. In both experiments nearly all acid, even at the highest acid load, disappeared (pH greater than 6). Inhibition of the duodenal mucosal bicarbonate secretion did not decrease the acid-neutralizing capacity of the human duodenum. In fact, the disappearance rate of acid at the highest acid load was a little greater when mucosal bicarbonate secretion had been inhibited than when not (10.3 +/- 0.5 vs. 9.2 +/- 0.2 mmol/h). The pancreaticobiliary secretion of bicarbonate, as judged by plasma secretin concentrations, increased, however, earlier when mucosal bicarbonate secretion had been inhibited than when not (3.7 vs. 3.0 pmol/l at an acid load of 6.0 mmol/h). This indicates that bicarbonate from the duodenal mucosa normally plays a role in the in lumen neutralization of acid in the human duodenum.

Duodenal Alkalinization Releases Secretin and Vasoactive Intestinal Polypeptide and Stimulates Exocrine Pancreatic Secretion in the Anesthetized Rat

The effect of various intraduodenal alkaline solutions (0.1 M NaHCO3, 0.1 M Na2CO3 and 0.025 M NaOH) on exocrine pancreatic secretion and the release of two peptides, secretin and vasoactive intestinal polypeptide, was studied in anesthetized rats. The flow rate of the pancreatic juice was stimulated up to a maximum of 179, 158 and 180% and the protein output up to 181, 131 and 162% (compared with basal) after duodenal perfusion of, respectively, 0.1 M NaHCO3, 0.1 M Na2CO3 and 0.025 M NaOH. Maximum increases in portal plasma secretin concentrations of 143, 146 and 190% and maximum increases in VIP of 116, 155 and 147% after, respectively, intraduodenal 0.1 M NaHCO3, 0.1 M Na2CO3, and 0.025 M NaOH were found. In conclusion duodenal alkalinization in the rat produces a pancreatic exocrine secretory response that may be partially ascribed to the effect of secretin and VIP.

Effect of Fatty Acid on Secretin Release and Cholinergic Dependence of Pancreatic Secretion in Rats

We investigated the effects of oleic acid in the duodenum on pancreatic exocrine secretion and plasma secretin, and determined the role of cholinergic dependence on pancreatic secretion and secretin release in response to oleic acid in anesthetized rats. Oleic acid emulsion (pH 6.5) in three different doses of 0.06, 0.25, and 1 mmol/h was infused intraduodenally for 1 h with or without intravenous administration of atropine in a dose of 100 micrograms/kg/h. Intraduodenal administration of oleic acid resulted in significant increases in pancreatic juice volume and bicarbonate output, in a dose-related manner (p less than 0.001). Plasma secretin concentration caused dose-dependent elevation (p less than 0.001) by oleic acid, which correlated very well with bicarbonate output in response to oleic acid (p less than 0.001). Atropine inhibited pancreatic secretion including juice volume and bicarbonate output stimulated by oleic acid in each dose, statistically significantly (p less than 0.05-0.01), but did not affect plasma secretin concentration. Thus, we conclude that oleic acid in the duodenum stimulates pancreatic secretion and endogenous secretin release in rats, and that secretin release is not influenced by the cholinergic tone, although pancreatic secretory response is inhibited significantly.

Effect of Plaunotol on Release of Plasma Secretin and Pancreatic Exocrine Secretion in Humans

Plaunotol, an acyclic diterpene alcohol is a new antiulcer agent derived from the leaves of the plau-noi plant. We investigated the effect of plaunotol on the release of endogenous secretin with radioimmunoassay and exocrine pancreatic secretion, using a dye dilution technique with polyethylene glycol 4,000 as a nonabsorbable marker in eight human volunteers. Intrajejunal administration of plaunotol (pH 6.5) in three different doses (80, 160, and 320 mg/30 min) resulted in significant increases in both plasma secretin concentration and pancreatic bicarbonate secretion in a dose-related manner (r = 0.819 and 0.701, p less than 0.001, respectively). Bicarbonate outputs produced by plaunotol correlated well with plasma secretin concentrations (r = 0.727, p less than 0.001). Amylase output was also increased significantly by plaunotol. However, the response was not dose-dependent from that of bicarbonate output. These results indicate that endogenous secretin is released by plaunotol in humans and suggest that the increased pancreatic bicarbonate secretion can be attributed to the increased plasma secretin concentration.

Plasma Gastrointestinal Hormones during Spontaneous and Induced Menstrual Cycles*

Plasma levels of secretin, vasoactive intestinal polypeptide (VIP), somatostatin (SRIH), motilin, and/or pancreatic polypeptide, as well as serum estradiol, progesterone, PRL, LH, FSH, and/or GH were measured during the follicular phase, midcycle, and luteal phase of a spontaneous menstrual cycle in eight women and during ovarian stimulation with clomiphene citrate/human menopausal gonadotropin and hCG for in vitro fertilization in nine women. Plasma SRIH concentrations were significantly (P less than 0.02) higher in the luteal phase of spontaneous menstrual cycles than in follicular phase and midcycle. Serum GH levels, however, did not change. Plasma motilin concentrations also were higher in the luteal phase than at mid-cycle (P less than 0.04). Plasma secretin, VIP, and pancreatic polypeptide concentrations did not change during the cycle. Throughout the spontaneous menstrual cycle we found significant positive correlations between plasma SRIH and serum progesterone (P less than 0.007; r = 0.5869), plasma motilin and serum progesterone (P less than 0.02; r = 0.5331), plasma secretin and serum estradiol (P less than 0.04; r = 0.4711), and plasma secretin and serum PRL (P less than 0.02; r = 0.5507). During ovarian stimulation both plasma secretin and VIP gradually increased to a peak on cycle days 0 and 1, respectively (day 0 = the day of hCG injection), whereas plasma SRIH did not change. Serum estradiol and PRL increased significantly, and both peaked on cycle day 1. During ovarian stimulation plasma secretin correlated significantly with serum estradiol (P less than 0.00001; r = 0.9333), serum PRL (P less than 0.03; r = 0.6521), and plasma VIP (P less than 0.03; r = 0.6534). In addition, plasma VIP and serum PRL both correlated significantly with serum estradiol (P less than 0.05; r = 0.6024 and P less than 0.04; r = 0.6384, respectively). These results indicate 1) a possible effect of progesterone on the release of SRIH and motilin during the spontaneous menstrual cycle; 2) the unaltered serum GH concentrations in the luteal phase of the spontaneous menstrual cycle despite elevated plasma SRIH levels are probably due to a stimulatory effect of both progesterone and motilin on GH release; and 3) the increase in plasma secretin and VIP concentrations during ovarian stimulation is probably secondary to the concomitant increase in serum estradiol and/or PRL. We suggest that estradiol and/or PRL beyond a certain threshold level stimulate the release of secretin, and possibly also VIP, into plasma.

Effect of Pancreatic juice and Trypsin on Oleic Acid-Stimulated Pancreatic Secretion and Plasma Secretin in Dogs

We have investigated a negative feedback mechanism in the intestinal phase of pancreatic exocrine secretion in dogs with gastric cannulas and Thomas duodenal cannulas in whom pancreatic juice was collected by cannulation of the main pancreatic duct. Intraduodenal infusion of oleic acid emulsion in a dose of 18 mmol/h resulted in a significant increase in pancreatic secretion of water, bicarbonate, and protein, which was accompanied by increased plasma concentrations of both secretin and cholecystokinin. Infusion of pancreatic juice or bovine trypsin into the duodenum significantly inhibited the oleic acid-stimulated pancreatic secretion. This inhibition coincided with a significant decrease in plasma secretin level, whereas plasma cholecystokinin concentration was not affected by either pancreatic juice or trypsin. Neither pancreatic secretion nor plasma secretin concentration was affected by intraduodenal administration of NaHCO3 solution. The trypsin-induced suppression of pancreatic secretion was prevented by intravenous administration of secretin in a dose that achieved a plasma secretin level comparable to that during the oleic acid administration. This study indicates that a negative feedback mechanism is operative in the intestinal phase of pancreatic exocrine secretion in dogs, and endogenous secretin plays a significant role in the mechanism.

Plasma secretin concentrations during normal human pregnancy, delivery, and postpartum.

Plasma concentrations of secretin were measured at 4-week intervals throughout eight normal pregnancies and again twice postpartum, and in another six women during parturition and the early postpartum period. Comparisons were made with levels in 16 normal non-pregnant women. Plasma secretin concentrations increased during pregnancy with maximum levels at 36 weeks. The increase was statistically significant from week 28 to 36, compared with non-pregnant levels. By 5 days after delivery plasma secretin levels were similar to the non-pregnant levels. No significant changes in plasma secretin were observed during delivery and early postpartum. The altered secretin levels may be of importance for heartburn in pregnancy, calcium metabolism, and the changes in renal haemodynamics.

Effect of pancreatic juice diversion on secretin release in rats

We investigated a possible role of secretin in the mechanism of exocrine pancreatic secretion after exclusion of pancreatic juice from the intestine in anesthetized rats. Diversion of pancreatic juice from the duodenum resulted in a significant increase in plasma secretin concentration from 0.76 ± 0.39 pM at 0 time to 3.09 ± 0.30 pM at 4 h after diversion. This increase in secretin coincided with a steady but significant increase in pancreatic secretion of volume and bicarbonate. Intraduodenal administration of fresh pancreatic juice completely reversed the diversion-induced increases in both plasma secretin and pancreatic secretion. Intravenous injection of a rabbit-antisecretin serum blocked the increase of pancreatic secretion during diversion of pancreatic juice from the duodenum. Thus, we conclude that endogenous secretin is involved in a hormonal mechanism regulating increased pancreatic exocrine secretion in pancreatic juice-diverted rats.

Plaunotol Stimulates Endogenous Secretin Release and Exocrine Pancreatic Secretion in Rats

The effect of the new antiulcer agent plaunotol on the release of endogenous secretin and the pancreatic exocrine secretion was investigated in anesthetized rats. In 48 rats with pancreatic and biliary diversion, continuous intraduodenal infusion of plaunotol in 3 graded doses (5, 20 and 80 mg/h/rat) resulted in significant increases in both circulating plasma secretin concentration and pancreatic exocrine secretion, including volume and bicarbonate output, in a dose-dependent manner (r = 0.655, p less than 0.001; r = 0.598, p less than 0.001; r = 0.436, p less than 0.01, respectively). The pancreatic bicarbonate output was closely correlated to plasma secretin concentrations (r = 0.631, p less than 0.001). Amylase output also increased after plaunotol administration, but not in a dose-dependent manner (r = 0.092, n.s.). These findings suggest strongly that the increase in pancreatic secretion of fluid and bicarbonate output was mainly due to increased endogenous secretin release resulting from plaunotol administration.

Effects of Oleic Acid and Oleyl Alcohol on Cholecystokinin and Secretin in Plasma and Pancreatobiliary Secretion

To evaluate the importance of the terminal carboxy group of the oleic acid molecule in the release of secretin and cholecystokinin (CCK) to plasma, six normal persons were stimulated twice with duodenal perfusates containing either 20 mM oleic acid or 20 mM oleyl alcohol. Oleic acid increased the pancreatic secretion of bicarbonate and amylase and the concentrations of secretin and CCK in plasma and provoked gallbladder emptying. Oleyl alcohol only increased the amylase output slightly, but significantly. It is concluded that the carboxy group of the fat molecule has an important role in triggering the release of secretin and CCK to plasma.

Effect of Low-Dose Exogenous Secretin and Somatostatin on Pentagastrin-Stimulated Gastric Acid Secretion in Man

The inhibitory effect of intravenous infusion of secretin (0.05 CU kg-1h-1) and somatostatin (60 pmol kg-1h-1), given alone or in combination, on pentagastrin-stimulated (100 ng kg-1 h-1) acid secretion was studied in 10 healthy subjects. Secretin inhibited acid secretion by 54% (p less than 0.05), and somatostatin inhibited by 70% (p less than 0.05). The combined infusion of secretin and somatostatin decreased acid output by 64% (p less than 0.05). The differences between the three groups were not significant (p greater than 0.05). Median plasma concentrations of secretin and somatostatin were of the same magnitude as seen after duodenal acidification. The present study did not demonstrate any interaction between secretin and somatostatin in the inhibition of gastric acid secretion.

Effect of low-dose exogenous secretin on pentagastrin- and meal-stimulated gastric acid secretion in humans

Intravenous infusion of secretin in a dose of 0.05 CU/kg/hr inhibited pentagastrin-stimulated (100 ng/kg/hr) acid secretion by 42% (P less than 0.05) abd meal-stimulated (10% peptone, pH 5.5) acid secretion by 33% (P less than 0.05) in 10 healthy subjects. Median serum gastrin concentration during peptone stimulation was reduced by 24% (P less than 0.05) during secretin infusion. Median plasma secretin concentrations were 6.0 and 5.2 pmol/liter, respectively. Since these secretin concentrations are of the same magnitude as those seen after duodenal acidification, it is concluded that secretin may participate in the physiological inhibition of gastric acid secretion.

Acid-independent release of secretin and cholecystokinin by intraduodenal infusion of fat in humans.

In order to clarify a possible role of fat content in the release of secretin and cholecystokinin by liquid nutritional supplements in humans, duodenal pH and plasma concentrations of secretin and cholecystokinin were studied during the intraduodenal infusion of Ensure, Vivonex, 10% Intralipid, and sodium oleate. Significant release of secretin was observed with Intralipid and sodium oleate, while significant release of cholecystokinin was observed with all four testing solutions. Duodenal pH was rarely below 4.5 during the infusion of Ensure, Intralipid, and sodium oleate. Duodenal pH was high, greater than 6.0, when plasma secretin and cholecystokinin levels were elevated during the administration of Ensure, Intralipid, and sodium oleate. We conclude that both secretin and cholecystokinin are released in response to fat solutions in the duodenum and that low duodenal pH was not responsible for either secretin or cholecystokinin release during intraduodenal infusions of Ensure, Intralipid, or sodium oleate.

Human secretin: Biologic effects and plasma kinetics in humans

The action of synthetic human secretin, which differs in two amino acid residues from porcine secretin, was compared with synthetic porcine secretin in 6 healthy volunteers. Pancreatic secretion was assessed by a marker perfusion technique and plasma secretin concentrations were assessed by a specific radioimmunoassay. Increasing doses of either human or porcine secretin produced increasing bicarbonate output (p < 0.01), whereas trypsin and lipase were not stimulated over basal. The highest doses of secretin induced a significant increase in pancreatic amylase secretion. The two secretin preparations were found to be equipotent with respect to pancreatic secretion and plasma kinetics. Significant increases of plasma secretin were observed after a steak meal in 15 volunteers (p < 0.001). When human secretin was infused at postprandial concentrations, significant increases in pancreatic bicarbonate output were observed (p < 0.05). We conclude (a) that the substitution of two amino acids in human secretin does not affect biologic activity and plasma metabolism of the compound; (b) secretin does not stimulate pancreatic enzyme secretion at physiologic concentrations; and (c) the stimulatory effects of secretin on pancreatic amylase remain to be elucidated. The study suggests that human secretin is a true hormone.