Effect of atropine on pancreatic responses to endogenous and exogenous cholecystokinin

The role of cholinergic innervation in endogenous release of cholecystokinin from the intestinal mucosa and in exocrine pancreatic secretion was examined by means of atropine administration in 3 chronic gastric-fistula and pancreatic-fistula dogs during pancreatic responses to various rates of intraduodenal amino acid mixture and to various doses of intravenous cholecystokinin producing equal rates of pancreatic protein secretion. Atropine infused in a dose of 100 µg/kg-hr caused a deep and prolonged decrease in pancreatic flow rate, protein and bicarbonate output, reaching a maximum of about 80% of the pre-atropine level of pancreatic secretion. The inhibition occurred regardless of the level of pancreatic response examined. Atropine also caused an inhibition of pancreatic responses to smaller doses of exogenous cholecystokinin but did not affect responses to larger doses. The maximal observed pancreatic protein secretion in response to intraduodenal administration of amino acids was about 80% of the highest response to cholecystokinin. This study suggests that the release of cholecystokinin from the intestinal mucosa might be cholinergically dependent.     

Effects of endogenous and exogenous secretin on plasma pancreatic polypeptide concentrations in dogs

Summary The effects of exogenous and endogenous secretin with or without intravenous glucose infusion upon islet hormone secretion were studied in four conscious mongrel dogs fitted with a duodenal fistula. Intravenous infusion of secretin for 1 h at doses of 0.5 and 4 U/kg raised plasma secretin concentrations to physiological and pharmacological levels respectively, without affecting plasma insulin and pancreatic polypeptide concentrations. In contrast, bolus injections of secretin at high concentrations produced significant increases of plasma insulin at 0.5 U/kg and 4 U/kg and of pancreatic polypeptide at 4 U/kg. Plasma glucagon did not change during intravenous infusion of low dose secretin (0.5 U · kg^–1 · h^–1), but decreased during infusion of 4 U · kg^–1 · h^–1 or bolus injection of secretin (0.5 U/kg). Intravenous infusion of glucose together with secretin (0.5 U/kg and 4 U/kg) did not affecf plasma insulin, glucagon, or pancreatic polypeptide levels significantly compared with the changes caused by glucose infusion alone. Intraduodenal instillation of HCl, which produced plasma secretin concentrations similar to those evoked by intravenous infusion of secretin (4 U · kg ^–1 · h^–1), led to a rise in plasma pancreatic polypeptide. It is concluded that the stimulatory effects of secretin on insulin and pancreatic polypeptide and the inhibitory effect on glucagon are pharmacological, and that increase of plasma pancreatic polypeptide after intraduodenal infusion of HCl is not mediated by endogenous secretin.     

Plasma secretin and pancreatic bicarbonate response to exogenous secretin in man.

The dose response of duodenal bicarbonate production during synthetic porcine secretin infusions was studied in six healthy volunteers and related to plasma secretin immunoreactivity. Secretin was infused in each individual at four different doses from 0-1 to 2-7 CU/kg/h, each infusion lasting for 60 minutes. Mean maximal bicarbonate secretion was 33 +/- 4 mEq/h. The secretin plasma level for half maximal bicarbonate response was estimated to be 22 pmol/l. As this level is reported to be achieved by intraduodenal acidification in man, it is concluded that secretin may well play a part in the control of duodenal pH.     

Effect of atropine on pancreatic bicarbonate output and plasma concentrations of immunoreactive secretin in response to intraduodenal stimulants

In conscious dogs with gastric and pancreatic Thomas fistulas we studied the effect of atropine (50 micrograms kg-1 intravenously) on pancreatic bicarbonate output and plasma concentrations of immunoreactive secretin in response to intraduodenal bolus injections of HCl (0.75 mmol), L-tryptophan (1 mmol), and sodium oleate (1 mmol). The 10-min integrated bicarbonate response to HCl was 1.7 times greater than the response to oleate and 2.8 times greater than that to tryptophan. Atropine significantly (p less than 0.05) depressed the 10-min integrated bicarbonate response to HCl, oleate, and tryptophan by 67%, 79%, and 61%, respectively. HCl and oleate, but not tryptophan, significantly increased plasma secretin concentrations over basal levels. Atropine did not significantly alter basal plasma concentrations of secretin or the 10-min integrated plasma secretin response to HCl and oleate. We conclude that 1) intraduodenal tryptophan stimulates pancreatic bicarbonate secretion by an atropine-sensitive mechanism, release of secretin not being involved, and 2) in the presence of atropine the depressed pancreatic bicarbonate response to HCl and oleate is not due to decreased release of endogenous secretin.     

Disappearance half-time of endogenous and exogenous secretin in dogs.

We have used a sensitive and specific radioimmunoassay to measurespectively. the disappearance half-times of exogenous porcine secretin and endogenous canine secretin in the dog and found them to be 2-45 and 2-85 minutes, respectively.     

Pancreatic responses to endogenous and exogenous gastrin in the dog

Serum gastrin and pancreatic secretion were measured in conscious Thomas fistula dogs during infusion of increasing doses of porcine gastrin, against a background of secretin. Dose-response relationships were calculated for the effects of gastrin on pancreatic secretion. Gastrin release was also measured after a test meal and after vagal stimulation with 2-deoxyglucose. Peak serum gastrin levels after these stimuli were less than the serum gastrin level associated with the minimal effective dose of gastrin. From the dose-response relationship of serum gastrin and pancreatic protein output, it was possible to calculate the protein output corresponding to the peak gastrin levels after 2-deoxyglucose or a meal. These were equivalent to 20-30% of the observed protein response to these stimuli. We conclude that gastrin plays at most a small part in the stimulation of pancreatic secretion after a meal and in response to 2-deoxyglucose. We also found that truncal vagotomy reduces pancreatic sensitivity to gastrin.     

Studies on exogenous and endogenous interaction of gastrin and secretin in a case of achalasia

Studies were carried out in a case of achalasia. Administration of secretin caused relaxation of the spastic condition of LES, and high levels of serum gastrin and lower levels of plasma secretin are suggested to be related with the abnormally spastic condition of LES in the patient.     

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.     

Influence of exogenous application of pancreatic extracts on endogenous pancreatic enzyme secretion.

The existence of negative feedback inhibition of human pancreatic enzyme secretion by proteases is controversially discussed. We have recently demonstrated that jejunal application of porcine pancreatic extracts, in a dose commonly used to treat digestive insufficiency, stimulated rather than inhibited, human pancreatic enzyme secretion. We have now studied the influence of duodenal application of high concentrations of either pure trypsin or porcine pancreatic extracts with trypsin-equivalent activity, on human pancreatic enzyme secretion. Twenty-three male volunteers were intubated with a gastric tube and a two-lumen jejunal tube to collect secretions separately via the first and third tubes and to perfuse either pure trypsin or porcine pancreatic extracts distal to the pylorus via the second tube. PEG-4.000 was continuously perfused via the second tube to correct for losses of volume. Volunteers received PEG alone during the first hour, phenylalanine during the second, PEG alone again during the third, and either phenylalanine together with trypsin or porcine pancreatic extracts during the fourth h. Activities of lipase, amylase, and chymotrypsin were measured in 15-min fractions. In addition, human lipase secretion was measured with an enzyme immunoassay, which does not crossreact with porcine lipase. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay, which utilizes amylase release by isolated rat pancreatic acini. Perfusion of the duodenum with phenylalanine caused a statistically significant stimulation of enzyme secretion. This stimulation could be inhibited by high concentrations of pure trypsin. In contrast, application of porcine pancreatic extracts, which contained the equivalent activity of trypsin, caused further increases of lipase secretion when compared to phenylalanine alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory mechanism of oxethazaine on release of endogenous secretin and pancreatic response in dogs

The mechanism by which oxethazaine inhibits hydrochloric acid stimulation of pancreatic secretion and the endogenous release of secretin was studied in six dogs prepared with pancreatic and gastric fistulae. Oxethazaine reduced both pancreatic secretion and plasma secretin concentration evoked by duodenal acidification, and the degree of inhibition was proportional to its dose. This drug did not inhibit the pancreatic secretion stimulated by the exogenous secretin. From kinetic analyses, it seems that oxethazaine acted as noncompetitive inhibitor of hydrogen ion on the chemoreceptors of the secretinreleasing cells in the duodenal mucosa. This may result in a decrease of secretin release from these cells and consequently of pancreatic secretion.     

Quantitation of tryptic responses to endogenous and exogenous stimulation in chronic pancreatitis

Using validated double-marker techniques to quantitate tryptic secretion we found that the mean 10-min output of trypsin in duodenal juice after a test meal was very similar to the peak 10-min output of trypsin after pancreozymin (2 Crick-Harper-Raper units/kg, Boots) both in controls as well as in non-diabetic patients with idiopathic chronic pancreatitis. These results show that the disproportionate reduction in mean tryptic activity after endogenous compared with exogenous stimulation in chronic pancreatitis is not due to impaired release of cholecystokinin-pancreozymin from the small intestine, nor to refractoriness of the pancreas to endogenously released hormone: instead, it is due to overdilution of secreted pancreatic enzymes because of accelerated gastric emptying, with or without gastric acid hypersecretion.     

Acute effect of captopril on aldosterone secretory responses to endogenous or exogenous adrenocorticotropin

The aldosterone secretory response to Captopril (12.5 mg, orally) was studied in five normal men. Endogenous ACTH and epinephrine secretion was stimulated by the induction of hypoglycemia. Normally this stimulus increases plasma cortisol, GH, aldosterone, and PRA. Administration of captopril resulted in a blunted plasma aldosterone response to hypoglycemia, but no concomitant blunting of the plasma cortisol response. The responses of other hormones, with the exception of PRA, were not affected. When exogenous ACTH was administered to the same men with and without captopril, the plasma aldosterone response was again blunted by captopril, while the plasma cortisol response was unaffected. We conclude that angiotensin II may be required for ACTH to stimulate aldosterone secretion. Alternatively, the possibility that captopril may selectively inhibit aldosterone secretion at the adrenal cellular level cannot be excluded.     

Effect of vagotomy and pyloroplasty on pancreatic dose-response curves to secretin in man

Pancreatic dose-response curves to secretin were obtained in 6 patients with duodenal ulcer before and after vagotomy and pyloroplasty. Pancreatic secretion was determined by a stepwise increase in secretin infused intravenously in progressively increasing doses, ranging from 0.1 to 3.6 units/kg/hr. Vagotomy and pyloroplasty did not cause significant changes in pancreatic dose-response curves for the volume flow and bicarbonate output, suggesting that the integrity of vagal nerves is of no major importance in the response of the pancreas to exogenous secretin.