Doses Of Secretin Research Articles

The role of secretin in the control of gastric secretion and emptying in the dog

It is well established that duodenal acidification strongly inhibits gastric acid secretion, gastric emptying rate and gastrin release. These effects are at least partly mediated via hormonal pathways, but it is not known whether they are mediated by the release of one peptide named in the past enterogastrone, or by several peptides acting together. The effects of duodenal acidification on gastric acid secretion and gastrin release can be reproduced by infusion of small doses of secretin and plasma secretin levels increase during duodenal acidification or after a meal. This peptide is thus the most probable candidate as an enterogastrone. It has however never been clearly shown that administration of low doses of secretin do decrease gastric emptying rate as well as acid secretion. Experiments were performed on four dogs with gastric fistulas. A peptone solution was infused into the stomach. The experiments were repeated during infusion of synthetic secretin. Our results indicate that infusion of low doses of secretin reproduce all the effects of duodenal acidification: a significant inhibition of gastric acid secretion, gastrin release and gastric emptying rate.

Effect of Enteric Hormone's on Sphincter of Oddi and Gastrointestinal Myoelectric Activity in Fasted Conscious Opossums

In this study we evaluated the effect of enteric hormones on sphincter of Oddi and gastrointestinal spike burst frequency in fasted conscious opossums. A chronic model for obtaining multiple long-term recording of sphincter of Oddi and gastrointestinal myoelectric activity was prepared in 12 animals by implanting bipolar electrodes in the gastric antrum, duodenum, sphincter of Oddi, jejunum, and ileum. Subsequently, 8-18 recording session, 6-8 h in length, were obtained in each animal. Each study was preceded by a 15-h fast. After recording two cycles of the interdigestive migratory myoelectric complex, a 60-min infusion of saline, cholecystokinin-octapeptide, pentagastrin, glucagon, or secretin was begun early in the quiescent period of duodenal activity, 10 min after termination of phase 3 of the migratory myoelectric complex activity. Cholecystokinin-octapeptide (10-80 ng/kg . min) and pentagastrin (25-200 ng/kg . min) increased sphincter of Oddi spike burst frequency while converting interdigestive gastrointestinal myoelectric activity to a fed-like pattern of continuous, irregular spike bursts. Glucagon at high doses of 500 and 1000 ng/kg . min depressed sphincter of Oddi and gastrointestinal spike burst activity, whereas lower doses of glucagon and secretin (3-12 CU/kg . h) had no effect. We conclude that in the opossum, relatively low doses of cholecystokinin-octapeptide and pentagastrin stimulate sphincter of Oddi and gastrointestinal spike burst activity while disrupting the cyclic pattern of sphincter of Oddi and gastrointestinal spike burst activity present during fasting. The physiological significance of these findings remains to be determined.

Dose response effects of atropine on pancreatic response to low doses of secretin: [formula omitted]. University of Essen, Germany

Dose response effects of atropine on pancreatic response to low doses of secretin: [formula omitted]. University of Essen, Germany

A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs

The endogenous peptides somatostatin and secretin are effective in the therapy of upper gastrointestinal tract bleeding and acute pancreatitis. The clinical effects may be partly brought about by changes in the regional blood flow. To evaluate the effects of somatostatin (50 and 100 μg/min over 6–8 min) and secretin (0.1 and 0.5 U · kg −1 · min −1 over 3–5 min) on tissue blood flow, particularly of the gastrointestinal tract, the tracer microsphere reference sample method was used in anesthetized dogs. Infusion of somatostatin significantly diminished gastric and pancreatic blood flow whereas no changes of duodenal and ileal blood flow could be obtained. Blood flow through spleen, kidneys and adrenal glands was increased but no changes were observed in the blood flow of other tissues. Cardiac hemodynamics remained unchanged. Secretin increased the blood flow of the duodenum, the kidneys and the adrenal glands and diminished gastric blood flow without changing pancreatic, ileal, hepatic, pulmonary and muscle blood flow. Cerebral, pituitary and myocardial blood flow was increased by a higher dose of secretin. It also evoked a slight but significant positive ino- and chronotropic effect. Since secretin and somatostatin differ in their respective effects on gastrointestinal blood flow it is suggested that the previously reported beneficial effects of both peptides on upper gastrointestinal bleeding cannot solely be attributed to changes in regional blood flow.

Effects of atropine on the action and release of secretin in humans.

Using two groups of volunteers, we investigated the effects of atropine on pancreatic secretion of bicarbonate, protein, and trypsin stimulated by secretin. Secretin given intravenously in graded doses of 0.03, 0.06, and 0.125 clinical units.kg-1.h-1 produced significant increases in pancreatic secretion of bicarbonate in a dose-related manner. Pancreatic secretion of bicarbonate and protein was significantly suppressed by intravenous atropine, despite the dose of secretin infused. Intrajejunal perfusion of HCl at a rate of 3.3 mM/h, producing plasma secretin concentration comparable with that of the postprandial state, resulted in significant increases in the pancreatic secretion of bicarbonate. The increase in the pancreatic secretion of bicarbonate and trypsin was significantly suppressed by atropine. However, atropine did not affect the increase in the plasma secretin concentration produced by jejunal acidification or intravenous secretin. These studies indicate that atropine inhibits the pancreatic effect but not the intestinal release of secretin.

Relationship between pancreatic and serum amylase in basal conditions and during stimulation in man: Report of a new intraoperative technique

The correlation between serum amylase and pancreatic amylase secretion was studied in two patients. Both patients underwent sphincterotomy, and the pancreatic duct was cannulated with a polyethylene tube. The tube was left in place for 15 to 21 days. The rate of amylase secretion over 7 days was studied in response to (1) a standard meal, (2) duodenal acidification, (3) scalar doses of cholecystokinin, (4) scalar doses of secretin, and (5) scalar doses of secretin with simultaneous infusion of cholecystokinin. Blood samples were collected during the tests to measure serum amylase. No significant correlation was shown between blood concentration and output of amylase in any of the tests. Our findings show that under normal conditions serum amylase levels are not influenced by pancreatic secretion and suggest that serum amylase concentration is not related to pancreatic exocrine secretion.

Calcium and parathyroid hormone behaviour after exogenous secretin infusion in man.

The response of serum calcium, PTH, CT and gastrin to an infusion of secretin (3 CU/kg/h) over a period of 90 min was studied in ten healthy males and two female patients with hypoparathyroidism. In the healthy males serum calcium, after a transient fall, significantly increased at 45 min after the onset of the infusion (P less than 0.001). Serum iPTH rose significantly within 5 min whereas serum CT and gastrin concentrations did not change. The two hypoparathyroid patients did not show any variations in either serum iPTH or calcium. These findings suggest that infusion of pharmacological doses of secretin into normal subjects modifies serum calcium, and that this change is due to PTH release.

Lack of CCK-like pancreatic stimulation by intraduodenal amino acids in the anesthetized cat

We have attempted to demonstrate a pancreatic secretory response to intraduodenal amino acids in the anesthetized cat. In four cats stimulated with supramaximal doses of secretin, protein concentrations in pancreatic juice were measured after intraduodenal bolus injection of various amino acids, IV CCK, or electrical stimulation of the vagus nerve. In addition, the duodenum was perfused with phenylalanine (50 mM) for 30 min in two cats, and the vagus nerve stimulated electrically for 15 min in one. In no case did amino acids produce pancreatic protein secretion, whereas CCK and vagal stimulation always did so. We conclude that this insensitivity to amino acids in the cat is a species difference from the dog and man.

Does basal cholinergic activity potentiate exogenous secretin for stimulation of pancreatic bicarbonate output in dogs?

In conscious dogs with gastric and pancreatic Thomas fistulas, we studied the effect of atropine sulfate (20 micrograms kg-1 h-1 intravenously) on bicarbonate output basally and in response to intravenous infusion of synthetic secretin (62.5, 125, 250, 500, 1,000 and 2,000 ng kg-1 h-1). We analyzed the data in an attempt to determine whether basal cholinergic activity potentiates the pancreatic bicarbonate response to secretin. Assuming that atropine suppresses all basal cholinergic activity, C (= bicarbonate response to basal cholinergic activity alone) was calculated by subtracting basal pancreatic bicarbonate output with atropine from that without atropine, S (= response to secretin alone) was calculated by subtracting basal pancreatic bicarbonate output with atropine from that in response to secretin with atropine. SwC was defined as the response to secretin acting simultaneously with (w) basal cholinergic activity and was calculated by subtracting basal pancreatic bicarbonate output with atropine from the response to secretin without atropine. If SwC was significantly greater than S + C (= sum of effects of stimulus alone and basal cholinergic activity alone) potentiation between basal cholinergic activity and secretin was assumed to exist. C was 30 +/- 9 mumol 15 min-1 for bicarbonate output. SwC of bicarbonate output was significantly (p less than 0.05) greater than S + C in response to the four lowest doses (62.5-500 ng kg-1 h-1) of secretin. We conclude that potentiation exists between basal cholinergic activity and low doses of exogenous secretin. Thus, basal cholinergic activity is an important modulator of pancreatic bicarbonate response to secretin.

Early increased pancreatic secretory capacity during alcohol adaptation in the dog.

Pancreatic secretion of bicarbonate and protein in response to graded secretin administration with and without concomitant 5 micrograms . kg-1 . h-1 atropine was examined in gastric and duodenal fistula dogs after 6 and 12 months of 2 g.kg-1.day-1 ethanol intake. Maximal responses of water and bicarbonate were significantly increased after 6 months of alcohol treatment compared with untreated animals, from 12.3 to 18.1 ml/10 min for volumes and from 1.76 to 2.63 meq/10 min for bicarbonate outputs. No further increase occurred during the following 6 months. The sensitivity to secretin was not changed, and the atropine dose did not affect the responses. The protein output in the untreated dogs was constant at 12.8 mg/10 min at all secretin doses and was reduced by 50% by concomitant atropine. Long-term administration of ethanol seemed to induce a dose-related increase of the protein response to secretin, the maximal output being 30.9 mg/10 min. The infused dose of atropine shifted the dose-response relationship to the right, thus making it more evident. Six months' alcohol treatment thus increased the secretory capacity of the pancreas in response to secretin. The increased volume and bicarbonate responses are best explained by the previously described neogenesis of ducts in alcohol-fed dogs. The increased protein response is assumedly due to the here-described appearance of acinar cell responsiveness to secretin.

Effect of hormones on cyclic AMP in dog pancreatic tissue and secretion

Secretin and cholecystokinin (CCK-PZ) were administered intravenously in graded doses to live anesthetized dogs. Pancreatic secretion and tissue biopsies were analyzed for cyclic AMP content. Both secretin and CCK-PZ caused an output of cyclic AMP into pancreatic secretion, secretin being a more potent stimulant than CCK-PZ. The concentration of cyclic AMP in the pancreatic juice increased with increasing doses of secretin but not with CCK-PZ. Tissue cyclic AMP content remained unchanged during infusion of either secretin or CCK-PZ. Infusion of aminophylline with secretin did not potentiate the action of secretin. It is concluded that synthesis of cyclic AMP in the dog pancreas is stimulated by both secretin and CCK-PZ and that the newly synthesized cyclic AMP is rapidly secreted into pancreatic juice, resulting in a steady content of tissue cyclic AMP.

Inhibition of Gastric Emptying in Humans by Secretin, the Octapeptide of Cholecystokinin, and Intraduodenal Fat

Intraduodenal fat is a potent inhibitor of gastric emptying. Neural and hormonal mechanisms are probably involved. Secretin and cholecystokinin are among the hormones known to be released by fat in the intestine. In this study we investigated the effect of the octapeptide of cholecystokinin, secretin, and intraduodenal oleate on the inhibition of gastric emptying of liquids in humans. On different days the gastric emptying of a 250-ml saline meal was studied in 6 healthy volunteers under the following conditions: (a) during graded doses of the cholecystokinin-octapeptide alone; (b) during graded doses of secretin; (c) during graded doses of secretin with a background of the cholecystokinin-octapeptide; and (d) during intraduodenal oleate perfusion. All the subjects were also studied for pancreatic enzyme secretion in response to the hormones and intraduodenal oieate. With a secretin background, the octapeptide of cholecystokinin was a potent stimulant of pancreatic secretion; while alone, only the highest dose significantly delayed gastric emptying. Secretin at doses of 2.5 pmol kg -1 · h -1 and higher significantly inhibited gastric emptying (p

The effect of secretin on gastric H+ and pepsin secretion and on urinary electrolyte excretion in man.

After an initial 40-min period of gastric suction, the gastric juice was collected for 12 30-min periods from 8 healthy young male students. During the first hour 30-min periods saline alone was infused, whereafter secretin in a dose of 0.05 CU/kg and h was given in the middle four 30-min periods and in a dose of 0.25 CU/kg and h for the final four 30-min periods. Urine was collected in three 2-h portions corresponding to each change of infusion procedure, and blood for determination of plasma secretin by a radioimmunoassay procedure was drawn at hourly intervals. Plasma secretin was unaltered both during the saline infusion and during the infusion of secretin in a dose of 0.05 CU/kg and h but rose during the infusion of 0.25 CU/kg and h. Compared with the mean 30-min output in the initial saline control period, gastrin pepsin secretion rose significantly in the third 30-min period, and gastric H+ output fell significantly in the fourth 30-min period of infusion of secretin in a dose of 0.05 CU/kg and h. During the higher secretin dose gastric output could not be evaluated owing to duodenogastric reflux. Urinary sodium excretion increased only during the infusion of secretin in a dose of 0.25 CU/kg and h, whereas secretin showed no effect on the urinary outputs of water, potassium, and solutes. The results of the present study indicate that secretin may play a physiological role in the regulation of gastric H+ and pepsin secretions, whereas its diuretic effect probably is a pharmacological effect only.

Effect of acetylcholine, gastrin, and glucagon alone and in combination with secretin and cholecystokinin on the secretion of the isolated perfused rat pancreas.

Dose-response curves of acetylcholine (ACh), gastrin, and glucagon given alone or in combination with a submaximal dose of secretin (S;' 5.0 U/h) plus cholecystokinin (CCK; 1.0 U/h) were studied in the isolated perfused rat pancreas. ACh (25 x 10-9 mol/h) increased the basal secretory flow ( mean +/- SEM: 1.19 +/- 0.22 microliter/min) by 693% and protein output (2.7 +/- 0.2 microgram/min) by 1726%. The protein secretion evoked by S plus CCK was further increased by ACh to a maximum of 26% whereas the volume secretion remained unaltered. Gastrin (100 ng/h) stimulated the protein output by 352% and, when combined with S and CCK, up to further 23% and the secretory flow by 37%. Glucagon evoked a significant (P less than 0.005) increase of the protein output, but decreased the volume as well as the protein output (by 43% and 32%, respectively; P less than 0.05) when it was combined with the tested doses of S and CCK.

Somatostatin 28: Comparison with somatostatin 14 for plasma kinetics and low-dose effects on the exocrine pancreas in dogs

The plasma kinetics of the synthetic tetradecapeptide somatostatin and of the newly characterized somatostatin 28 were comparatively assessed in dogs, using a radioimmunoassay system in which both peptides are equally recognized. The metabolic clearance rate, distribution volume, and calculated half-life were 157.0 ± 34.9 ml kg−1 · min−1, 301 ± 76.6 ml/kg and 1.34 ± 0.07 min for the tetradecapeptide infused at progressively increasing doses of 242–2424 pmol kg−1 · h−1, against 28.1 ± 7.5 ml kg−1 · min−1 (p < 0.02), 165 ± 76.4 ml/kg (p > 0.02) and 3.64 ± 0.98 min (p < 0.02) for somatostatin 28 infused at doses of 25–126 pmol kg−1 · h−1. Gel filtration of peripheral plasma sampled while infusing the largest dose of each peptide showed that for periods up to 40 min, there was no evidence of conversion into the opposite form. When administered intravenously for 1 h, somatostatin 14 at doses of 180 and 210 pmol kg−1 · h−1, and somatostatin 28 at doses of 30 and 40 pmol kg−1 · h−1, induced increments of the somatostatin concentration in peripheral plasma that were similar to those recorded after ingestion of a regular meal in the same dogs. These infusions significantly inhibited the volume, bicarbonate output, and protein output of the pancreatic response to 0.25 CU kg−1 · h−1 secretin plus 20 ng kg−1 · h−1 caerulein in the same animals. These results indicate that somatostatin 28 is cleared from plasma at a slower rate than the tetradecapeptide in dogs. Hence, near-physiologic increments of plasma somatostatin concentration, when reproduced by infusing the exogenous peptides, require on a molar basis four to six times less somatostatin 28 than somatostatin 14. Under such conditions, both peptides appear capable of inhibiting the response of the exocrine pancreas to submaximal doses of secretin plus caerulein.

Effect of secretin on parathyroid hormone and calcitonin secretion.

The effect of secretin on secretion of parathyroid hormone (PTH) and calcitonin (CT) was evaluated by both in vitro and in vivo techniques. In in vitro studies with bovine parathyroid tissue, Secretin-Boots caused significant dose-related increases in PTH secretion. In in vitro studies with rat thyroparathyroid tissue, Secretin-Boots caused significant increases in both PTH and CT secretion. Infusion of Secretin-Boots or of synthetic secretin in biologically equivalent doses into rats caused similar increases in secretion of PTH and of CT. Infusion of multiple doses of synthetic secretin revealed a dose-related stimulation of both PTH and CT secretion. Infusion of Secretin-Boots into normal human subjects caused prompt and progressive significant increases in secretion of both PTH and CT, with return to baseline values within 90 min after termination of the infusion. These data suggest that secretin can stimulate hormonal secretion by parathyroid and thyroid C cells and that secretin may play a modulating role in the secretion of both PTH and CT.

Response of the exocrine pancreas to graded doses of secretin in calcium-treated and normal dogs

Persisting modifications induced by repeated intravenous calcium infusion (acute hypercalcaemia) were investigated in 6 Thomas fistula dogs: 4 controls and 4 calcium-treated dogs, two of which were studied as controls. 1. (a) The pancreatic response to graded doses of synthetic secretin (water and bicarbonate outputs) was significantly reduced in calcium-treated dogs when compared with controls. As both the D 50 for secretin-induced response increased, and the maximal secretory response decreased, it may be concluded that calcium treatment decreased the sensitivity of duct cells to secretin and reduced their secretory capacity. 2. (b) A similar dose—response relationship was observed between secretin and pancreatic calcium outputs in controls and calcium-treated dogs. The secretin induced pancreatic calcium secretion was independent of protein secretion the latter not being modified by secretin. Thus it may be assumed that the secretory fluid calcium originated from a protein independent pool and had a dose-dependent relationship to secretin. 3. (c) These results help to illuminate the aetiology of chronic pancreatitis induced by acute hypercalcaemia and by hyperparathyroidism.

Thyrotropin-releasing hormone inhibits pancreatic enzyme secretion in humans

Recent studies have shown that thyrotropin-releasing hormone is present in gastrointestinal tissues and has effects on gastrointestinal motility and secretion. In the present study, we have investigated in healthy subjects the effects of various doses of thyrotropin-releasing hormone on secretin-cholecystokinin-stimulated pancreatic secretion. Intravenous infusion of thyrotropin-releasing hormone at doses of 4, 20, and 100 μg/30 min, administered during a constant pancreatic stimulation with secretin (0.5 Clinical Units/kg/h) and cholecystokinin (0.5 Ivy dog units/kg/h), produced a significant decrease in lipase and chymotrypsin secretion without affecting volume and bicarbonate secretion. The decrease appeared immediately with the lowest dose of TRH employed, and was progressively more marked with increasing doses of the hormone. Compared with the control experiments, the maximal inhibition of lipase output reached −17.6%, −37.2%, and −43%, and the maximal inhibition of chymotrypsin output −18.2%, −39.3%, and −44.9%, for the three doses of thyrotropin-releasing hormone employed, respectively. It is concluded that TRH has a marked inhibitory effect on the enzymatic component of the pancreatic secretion stimulated by submaximal doses of secretin and cholecystokinin. The physiologic importance of this effect remains to be defined.

Secretin is an enterogastrone in the dog.

To determine the physiological significance of secretin on gastric secretion, effects of normal rabbit serum (control) and rabbit antisecretin serum (anti-S) on meat meal-stimulated gastric secretion of acid and pepsin from vagally innervated fundic pouches were studied in four dogs with gastric fistulas. The intravenous administration of control serum did not affect the postprandial rise in plasma secretin concentration, whereas intravenous anti-S virtually eliminated the circulating plasma secretin. Both plasma gastrin concentration and acid output following intravenous anti-S were significantly greater than those following intravenous control serum. However, pepsin outputs in the two groups of experiments were not significantly different. In the same dogs in the fasting state, during intravenous infusion of secretin in doses of 0.06 and 0.125 U . kg-1 . h-1, the acid output stimulated by intravenous human synthetic gastrin in a dose of 0.25 micrograms . kg-1 . h-1 was significantly less than that during intravenous saline. The studies indicate that secretin in a physiological dose can inhibit postprandial release of gastrin and gastric secretion of acid, and thus secretin is an enterogastrone in the dog.

Effect of secretin on pancreatic duct pressure, resistance to pancreatic flow, and duodenal motor activity in the dog.

To determine the effect of graded doses of intravenously administered secretin on the relationships among pancreatic duct and duodenal pressures and duodenal motor activity, three dogs were surgically provided with three indwelling duodenal catheters and a permanent pancreaticodochocutaneous catheter. The proximal duodenal catheter was located within the first portion of the duodenum and was used to infuse a nonabsorbable marker. The middle catheter was positioned 5 cm distally so that its open tip was at the level of the pancreatic duct orifice, was water filled and utilized to measure duodenal pressures. Samples of duodenal contents were recovered from the third catheter which was 10 cm distal to the pancreatic ductal orifice. Dogs were studied for 8 hr. Saline was given intravenously for 1 hr at the beginning and end of the study and for 2 hr between two 2-hr periods of secretin administration. Secretin was administered at doses of 0.75, 1.5, 3.0 units/kg/hr. Only two doses of secretin, given in random order, were tested each day. Secretin significantly (P<0.05) reduced pancreatic duct pressure, duodenal pressure, and frequency of duodenal phase-III motor activity and increased duodenal volume flow. All of the responses were dose-related. The highest amounts of constantly infused secretin decreased pressures and increased duodenal volume flow compared with the lowest amount (P<0.05),. Moreover, calculations of resistance to pancreatic flow, the diameter of the pancreatic ductal opening, and the area of the opening indicated that secretin dilated the opening of the pancreatic duct and decreased the resistance of the flow of pancreatic juice into the duodenum as the dose of secretin was increased. Thus, it appears that a pancreatic ductal sphincter mechanism responsive to secretin is present in the dog.