Plasma Secretin Levels Research Articles

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading.

During acute base excess, the renal collecting duct β -intercalated cells ( β -ICs) become activated to increase urine base excretion. This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFTR) expressed in the apical membrane of β -ICs. The signal that leads to activation of this process was unknown. Plasma secretin levels increase during acute alkalosis, and the secretin receptor (SCTR) is functionally expressed in β -ICs. We find that mice with global knockout for the SCTR lose their ability to acutely increase renal base excretion. This forces the mice to lower their ventilation to cope with this challenge. Our findings suggest that secretin is a systemic bicarbonate-regulating hormone, likely being released from the small intestine during alkalosis. The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β -intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β -intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid-base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.

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.

MEK inhibits secretin release and pancreatic secretion: roles of secretin-releasing peptide and somatostatin.

We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.

Endogenous nitric oxide mediates pancreatic exocrine secretion stimulated by secretin and cholecystokinin in rats.

Nitric oxide (NO) is one of the important biologic mediators in regulation of gastrointestinal (GI) functions, but the influence of NO on the release of secretin and cholecystokinin (CCK) and exocrine pancreatic secretion has not been adequately investigated in the rat. The aim of this study was to determine the role of NO on endogenous and exogenous secretin- or CCK-stimulated pancreatic exocrine secretion both in anesthetized and conscious rats. Experiments were carried out in four different groups of rats with duodenal pancreatobiliary cannulas and jugular vein catheters. Group 1: During duodenal infusion of 0.05N HCl or 15% casein (pH 7.0), N-nitro-L-arginine (NNA), an inhibitor of NO-synthase in graded doses (2.5, 5, 10 mg/kg/h), was infused intravenously. Group 2: One hour after starting intravenous secretin at 5 pmol/kg/h or intravenous CCK-8 at 0.06 microg/kg/h, NNA in graded doses was administered intravenously. Group 3: In conscious rats, NNA (5 mg/kg/h) was given intravenously for 1 hour after a meal. Group 4: L-Arginine at 100 mg/kg/h was infused intravenously during the period of NNA (5 mg/kg/h) infusion in groups 1, 2, and 3. Pancreatic juice was collected at 30-minute intervals to measure volume, as well as output of bicarbonate and protein. At the end of the experiment, plasma secretin, vasoactive intestinal polypeptide (VIP) and CCK levels were determined by radioimmunoassay (RIA). NNA dose dependently inhibited the pancreatic secretion of fluid and bicarbonate stimulated by duodenal acidification, exogenous secretin, and a meal. NNA dose dependently inhibited the pancreatic secretion of protein stimulated by duodenal infusion of casein, exogenous CCK, and a meal. L-Arginine significantly reversed the NNA-induced inhibition of pancreatic secretion in all experiments. NNA did not alter significantly the plasma levels of secretin, VIP, and CCK. Our results indicated that endogenous NO plays a significant role in the regulation of pancreatic exocrine secretion stimulated by secretin and CCK. However, NO does not influence the release of secretin, VIP, or CCK in the rat.

Canine pancreatic juice stimulates the release of secretin and pancreatic secretion in the dog.

A secretin-releasing factor (SRF) was found in canine pancreatic juice that increases plasma secretin and stimulates pancreatic secretion in rats, suggesting that a positive feedback mechanism may be involved in the regulation of pancreatic secretion. In the present study, we investigated to determine whether or not SRF releases endogenous secretin and stimulates exocrine pancreatic secretion in conscious dogs. Fresh pancreatic juice was collected from four dogs by intravenous administration of secretin at 0.5 microg. kg(-1). h(-1) and CCK at 0.2 microg. kg(-1). h. The juice was boiled for 10 min at 100 degrees C. Experiments were carried out in phase I of spontaneous cycle of interdigestive pancreatic secretion. The testing solutions were infused intraduodenally in separate experiments: NaHCO3 solution (0.1 M, 4.5 ml/min, 60 min), a corn oil (Lipomul, 2 ml/min, 10 min), boiled pancreatic juice (BPJ, 4.5 ml/min, 60 min), and mixture of BPJ and Lipomul. Pancreatic secretion of fluid and bicarbonate was significantly increased by either BPJ or a mixture of BPJ and Lipomul (34- and 31-fold or 41- and 38-fold, respectively). Plasma secretin level also significantly increased by 164.7 +/- 13.4% and 223.1 +/- 35.0%, respectively, from basal concentration of 1.7 +/- 0.5 pM. In contrast, neither bicarbonate solution nor Lipomul influenced the plasma secretin level or pancreatic secretion. In addition, when Lipomul was incubated with BPJ, no fatty acid was produced. Thus the increased pancreatic secretion in the dog infused with a combination of BPJ and Lipomul was caused by SRF in BPJ, which released endogenous secretin. Moreover, the increases by BPJ of both plasma secretin level and bicarbonate secretion were completely blocked by intravenous administration of an antisecretin antibody in these dogs. The observations suggest that SRF in pancreatic juice exerts a positive feedback effect on exocrine pancreatic secretion that is mediated by the release of secretin in the interdigestive state in dogs.

Duodenal acid-induced gastric relaxation is mediated by multiple pathways.

In this study, we used an in vivo anesthetized rat model to investigate the mechanisms responsible for duodenal acid-induced inhibition of gastric motility. Intraduodenal infusion of HCl produced a rate-dependent decrease in intragastric pressure. Infusion of HCl at 2 ml/h produced a physiological plasma secretin level and elicited a decrease in intragastric pressure of 3.0 +/- 0. 2 cmH20. Infusion of rabbit secretin antiserum reduced the acid-induced inhibition of gastric motility by 85 +/- 5%, suggesting mediation mainly by endogenous secretin. Administration of the cholecystokinin (CCK)-A antagonist MK-329 caused only a modest 10 +/- 3% reduction in gastric relaxation, whereas the serotonin antagonist ICS-205930 had no effect. In contrast, immunoneutralization with the secretin antibody caused only a 15% reduction in the relaxation evoked by a higher rate of HCl infusion (3 ml/h), whereas MK-329 and ICS-205930 caused a 20 +/- 4% reduction and no reduction, respectively. Bilateral truncal vagotomy or perivagal application of capsaicin completely abolished gastric relaxation in response to low rates (1-2 ml/h) of 0.1 N HCl infusion but only partially affected gastric relaxation in response to a higher infusion rate (3 ml/h). These observations indicate that multiple pathways mediate the duodenal acid-induced inhibition of gastric motility. At low rates of HCl infusion, gastric relaxation is mediated primarily by endogenous secretin, which acts through vagal afferent pathways. At higher rates of HCl infusion, gastric relaxation is mediated by endogenous secretin, CCK, and possibly by the direct action of HCl on vagal afferent pathways or yet unidentified neuropathways.

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.

Elevation of plasma peptide YY and pancreatic juice hypersecretion following massive small bowel resection in the rat.

To clarify a physiological role of endogenous peptide YY(PYY) on pancreatic exocrine secretion, gastrointestinal transit and bile flow, a hyper-PYY-emia model was constructed by performing a massive small bowel resection using rats. (1) 75% resection of the small intestine was performed at its distal side. Two weeks after surgery, these rats were fed a liquid meal, and intestinal transit of contents was observed and plasma PYY and secretin concentrations were measured by radioimmunoassay. (2) Two weeks after the same surgery, a liquid meal was infused into the duodenum, and both pancreatic juice and bile were collected separately under general anesthesia. Transit of the intestinal contents from the pyloric ring, plasma CCK concentrations, pancreatic juice flow, amylase output, and bile flow were determined. Hyper-PYY-emia occurred following surgery both at fasting and after feeding, accompanied by retardation of gastrointestinal transit, increase of pancreatic juice flow and decrease of bile flow. Plasma secretin levels were elevated slightly, while CCK levels remained unchanged. In conclusion, massive small bowel resection is a useful model to induce hyper-PYY-emia in rats. It is considered that, in a malnutritional state after small intestinal resection, a colonic regulatory mechanism, via humoral factors such as PYY, participates in the feedback regulation of proximal intestinal as well as of pancreatic function.

Pancreatic enzyme secretion in response to test meals differing in the quality of dietary fat (olive and sunflowerseed oils) in human subjects.

The aim of the present study was to investigate in human subjects whether or not the ingestion of two liquid meals that differed only in their fatty acid composition (due to the addition of olive oil (group O) or sunflowerseed oil (group S) as the source of dietary fat) would lead to differences in the pancreatic enzyme activities secreted into the duodenum. The experiments were performed in eighteen cholecystectomized subjects who, during the 30 d period immediately before surgery, modified their habitual diets in such a way that their fat composition would reflect, as far as possible, that of the experimental meals. Lipase (EC 3.1.1.3), colipase, amylase (EC 3.2.1.1), chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) activities were measured in duodenal contents aspirated before and after the ingestion of the test meals. The plasma levels of secretin and cholecystokinin (CCK) were also examined. Duodenal enzyme activities were similar in resting conditions. No significant differences were revealed in postprandial enzyme activities, except for lipase activity, which was higher in group O, probably in relation to the greater plasma CCK concentrations observed in this group. In the absence of enzyme output data, we should not exclude the possibility that the type of dietary fat will affect human pancreatic enzyme secretion to a greater extent than is evident from the present study, for instance through a flow-mediated effect, as we previously observed in dogs.

Feedback Regulation of Pancreatic Exocrine Secretion in Minipigs

Background: The mechanism behind the possible feedback regulation of pancreatic exocrine secretion is not well understood. Methods: Thirteen minipigs were prepared with fistulas to the pancreatic duct and the duodenum. Peripheral venous blood was obtained for determination of secretin and cholecystokinin (CCK) levels. Four different experiments were performed: 1) diversion and reinfusion of pancreatic juice; 2) intraduodenal infusion of NaHCO3 solution, with the same volume, bicarbonate concentration, and osmolality as the collected pancreatic secretion, and reinfusion of pancreatic juice; 3) reinfusion of pancreatic secretion for 1 h before and 2 h after a meal; and 4) diversion of pancreatic secretion and intraduodenal infusion of NaHCO3 solutions before and after a meal. Results: Reinfusing pancreatic juice significantly decreased pancreatic juice volume and bicarbonate output and slightly decreased the level of secretin in plasma. Alternating infusions of substitute NaHCO3 and pancreatic juice did not change pancreatic output of bicarbonate and protein, nor did it change the CCK and secretin levels in plasma. Replacing pancreatic juice with intraduodenal NaHCO3 infusions during a meal did not significantly modify the pancreatic secretion of bicarbonate and protein or the hormonal levels in blood. Conclusions: A negative feedback regulation of pancreatic exocrine secretion is present in starved minipigs. Duodenal acidity and plasma levels of secretin seem to be of importance, whereas duodenal enzymatic activity and the level of CCK in plasma probably are not. A postprandial negative feedback regulation through duodenal enzymatic activity and release of CCK into blood could not be shown.

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.

Negative feedback regulation of pancreatic exocrine secretion in guinea pigs.

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.

Cholinergic Pathways Are Involved in Secretin and VIP Release and the Exocrine Pancreatic Response After Intraduodenally Perfused Acetic and Lactic Acids in the Rat

The response of the exocrine pancreas to intraduodenal perfusion of acetic and lactic acids in normal and previously atropinized rats was studied. Secretin and vasoactive intestinal peptide (VIP) plasma levels in portal plasma were also measured. Intraduodenal perfusion of both acetic and lactic acids significantly stimulated flow rate (from 0.29 +/- 0.03 microliters/min to a maximum of 1.06 +/- 0.08 microliters/min after acetic and from 0.35 +/- 0.05 microliters/min to a maximum of 1.13 +/- 0.12 microliters/min after lactic acid perfusion) and protein output (from 11.16 +/- 2.33 micrograms/min to a maximum of 35.1 +/- 7.4 micrograms/min after acetic and from 8.98 +/- 0.95 micrograms/min to a maximum of 22.5 +/- 1.3 micrograms/min after lactic acid perfusion). Atropine treatment significantly inhibited pancreatic flow rate and protein output after acetic acid perfusion, but no inhibition of flow rate and a slight decrease in the protein output after lactic acid perfusion were seen. With respect to plasma peptide concentrations, significant increases in secretin and VIP levels were found after perfusion of both organic acids; atropine administration significantly decreased plasma secretin levels after acetic acid administration although it did not affect plasma VIP concentrations. By contrast, atropine significantly increased plasma secretin levels, but significantly lower values of plasma VIP concentrations were observed after lactic acid perfusion. Therefore, cholinergic mechanisms are involved in the release of secretin and VIP and different types of control of exocrine pancreatic secretion occur, depending on the features of the intraduodenal stimulant.

Duodenal acidification and secretin, but not intraduodenal fat, inhibit human gastric acid secretion via prostaglandins

Background/Aims: Acid and fat in the duodenum inhibit gastric acid secretion and increase plasma secretin. The role of prostaglandins and secretin in the inhibition of gastric acid secretion by duodenal infusion of hydrochloric acid and fat in healthy human volunteers was studied. Methods: Gastric acid secretion was submaximally stimulated with intravenous pentagastrin followed by duodenal infusion of 0.1 N hydrochloric acid, oleic acid, or intravenous secretin. To inhibit endogenous prostaglandins, the protocol was then repeated after indomethacin treatment. Results: Duodenal fat infusion inhibited acid secretion 80% ± 5% and was unaffected by indomethacin treatment. Intraduodenal acidification inhibited acid secretion by 43% ± 8% and was reduced by indomethacin treatment to 15% ± 4% (P < 0.01). Similarly, intravenous secretin inhibited acid secretion by 34% ± 3%, which was decreased to 13% ± 6% by indomethacin treatment (P < 0.01). The increase in plasma secretin levels after intraduodenal hydrochloric acid treatment was significantly greater than that observed with intravenous secretin or introduodenal oleic acid treatment; all were within the physiological range. Acid in the duodenum releases secretin, which inhibits gastric acid secretion at least in part via prostaglandins. In contrast, fat in the duodenum strongly inhibits gastric acid secretion via a nonprostaglandin pathway. Conclusions: Secretin is the predominant mediator for the inhibition of human gastric acid secretion induced by the presence of acid, but not fat, in the duodenum.

Effect of intraduodenai infusion of tocamphyl on pancreatic exocrine secretion and gastrointestinal hormone release in rats

Tocamphyl is a synthetic choleretic that is derived from a root extract of Curcuma longa, L. We investigated the effect of tocamphyl on pancreatic exocrine secretion and bile flow, and on the release of some gastrointestinal hormones, by administering it intraduodenally using anesthetized rats. Tocamphyl stimulated pancreatic exocrine secretion in terms of volume and amylase output in a dose-related manner. Neither a CCK-receptor antagonist, CR1505 (loxiglumide), nor atropine sulfate infused intravenously suppressed the stimulatory effects of tocamphyl on pancreatic exocrine secretion and bile flow. The stimulatory effect on bile flow was stronger than that on pancreatic exocrine secretion. Plasma secretin levels were augmented with the increasing doses of tocamphyl, but CCK levels were not. These results indicate that intraduodenally administered tocamphyl stimulates pancreatic exocrine secretion and bile flow, and suggest that the stimulatory action is, at least in part, mediated by secretin, but not by either CCK or the cholinergic pathway.

Duodenal mucosal bicarbonate secretion in pigs is accompanied by compensatory changes in pancreatic and biliary HCO3- secretion.

The purpose of the study was to examine the effect of stimulation and inhibition of duodenal mucosal bicarbonate secretion on pancreatic and hepatic bicarbonate secretion in response to acid. The effect of inhibition (indomethacin) or stimulation (misoprostol) of duodenal mucosal bicarbonate secretion on pancreatic and biliary bicarbonate secretion in response to intraduodenal infusion of HCl or intravenous infusion of secretin was studied in anaesthetized pigs. The hepatic and pancreatic response to exogenous secretin was not significantly altered by stimulation/inhibition of duodenal bicarbonate secretion. However, pancreatic and biliary bicarbonate secretion in response to duodenal acidification was significantly augmented by inhibition of duodenal mucosal bicarbonate secretion; conversely, it was reduced by stimulation of duodenal bicarbonate secretion. The increase in plasma secretin levels in response to duodenal acidification was reduced by stimulation and augmented by inhibition of duodenal mucosal bicarbonate secretion. Duodenal mucosal bicarbonate secretion can serve as a modulator of both pancreatic and biliary bicarbonate secretion in response to luminal acidification, possibly through regulation of the release of secretin.

Dose-response effect of intraduodenal HCl on exocrine pancreatic secretion, portal secretin, and VIP plasma levels in anesthetized rats.

In anaesthetized rats, a dose-dependent effect of different intraduodenal HCl loads (0.6, 1.2, 6 and 12 mmol/h) on exocrine pancreatic secretion and plasma levels of secretin and VIP has been observed. The flow rate of pancreatic juice showed a significant increase at all the doses used; the integrated percentage response (IPR) of flow were 359%, 595%, 894% and 1371% for, respectively, 0.6, 1.2, 6 and 12 mmol/h. The increase of protein output only achieved statistical significance at HCl loads of 6 mmol/h or more; the IPR of protein output were 153%, 305%, 320% and 420% for, respectively, 0.6, 1.2, 6 and 12 mmol/h HCl. Portal levels of secretin and VIP were measured by specific radioimmunoassays. Significant increase of secretin concentration was observed at HCl loads of 1.2 mmol/h or more, whilst VIP levels only increased significantly after intraduodenal HCl load of 6 mmol/h or more. The IPR of secretin release were 180%, 203%, 280% and 322% for, respectively, 0.6, 1.2, 6 and 12 mmol/h HCl and IPR of VIP release were 3%, 20%, 244% and 315% for, respectively, 0.6, 1.2, 6 and 12 mmol/h HCl. Our results suggest that secretin may play a more prominent role than VIP in stimulating exocrine pancreatic secretion in response to intraduodenal loads of acid in this species.

Secretin and portal blood flow.

Using a duplex Doppler technique, we investigated the effect of low doses of secretin on the portal blood flow. In eight healthy volunteers successive intravenous secretin infusions of 0, 8, and 32 pmol x kg-1 x h-1 resulted in proportional increases in plasma secretin levels. The portal venous flow, however, was unaffected. A bolus injection of 930 pmol of secretin caused plasma secretin levels to increase 100-fold, whereas blood flow in the portal vein increased only by a factor three. This suggests that secretin in the present dose range is of no quantitative importance as a regulator of portal venous flow under physiologic conditions.

Inhibitory action of peptide YY on pancreatic secretion is independent of secretin.

The purpose of this study was to characterize the effect of peptide YY (PYY) on acid-stimulated pancreatic bicarbonate secretion and to determine whether PYY affects the release of secretin in response to intraduodenal infusion of acid. Six dogs were prepared with gastric and pancreatic cannulas. In study 1, graded doses of hydrochloric acid (HCl) (3, 6, 12, and 24 mEq/h) were given intraduodenally alone or in combination with intravenous PYY (400 pmol/kg.h). In study II, and ED50 of intraduodenal HCl (6 mEq/h) was given alone or in combination with graded doses of PYY (12.5, 25, 50, 100, 200, and 400 pmol/kg.h, i.v.). Bicarbonate output was significantly inhibited during PYY infusion at 200 and 400 pmol/kg.h, but plasma secretin levels were unchanged. The calculated maximal response for bicarbonate secretion (5.1 +/- 1.3 mEq/15 min) was significantly reduced by PYY (2.1 +/- 0.7 mEq/15 min). We concluded that PYY can inhibit acid-stimulated pancreatic bicarbonate secretion without affecting the release of secretin. The mechanism of the inhibitory effect of PYY on acid-stimulated pancreatic bicarbonate secretion is compatible with a noncompetitive type of inhibition.

Hormonal Control of Pancreatic Secretion by Intrajejunal HCl

To elucidate the role of hormones in the control of pancreatic secretion, we developed, in seven dogs, a model of total extrinsic denervation of the jejunoileum by autotransplanting this segment of bowel. A Thomas-like cannula was placed into the stomach, the duodenum (to collect pure pancreatic juice), and the proximal part of the jejunum. Thus, intestinal stimulants could only stimulate the pancreas via release of humoral (= hormonal) mediators. Seven control dogs received only the three fistulas. After recovery, dose-response curves of pancreatic bicarbonate and protein response to perfusion of the extrinsically denervated or innervated jejunoileum with HCl (1.5 to 48 mmol h-1) were performed with and without atropine (14 nmol kg-1 h-1 i.v.). Plasma levels of secretin were determined by radioimmunoassay. The maximal bicarbonate output occurred in response to 24 mmol h-1 of HCl and was significantly (p less than 0.05) higher in intact as compared to denervated animals. Atropine only significantly depressed the bicarbonate response to HCl in dogs with a denervated jejunoileum. HCl caused a dose-dependent increase in plasma levels of secretin, which was not altered by denervation and/or atropine. Irrespective of the innervation of the small bowel, pancreatic protein output was only significantly stimulated above basal when high loads (12-48 mmol h-1) of HCl were given. Atropine significantly reduced these responses.(ABSTRACT TRUNCATED AT 250 WORDS)