Intraduodenal Infusion Of HCl Research Articles

Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats.

Whether cholecystokinin (CCK) has a direct action on duct cells and the role of CCK-A receptor in bicarbonate secretion were examined by comparing the results obtained from OLETF (CCK-A receptor-deficient rats) and control (LETO) rats. Rats were prepared with cannulae for draining bile and pancreatic juice separately, with two duodenal cannulae and an external jugular vein cannula. The experiments were conducted without anesthesia. The responses of bicarbonate secretion to intravenous infusion of CCK, acetyl-beta-methylcholine (Ach), and 2-deoxy-D-glucose (2DG), and to intraduodenal infusion of HCl and a liquid meal were examined. To examine the synergistic effect between CCK and secretin, the effect of CCK during a background secretin infusion was examined in LETO rats. CCK did not stimulate bicarbonate secretion in either strain, nor in LETO rats with secretin infusion. When gastric acid secretion was prevented by administration of omeprazole, Ach did not increase bicarbonate secretion, but 2DG did in both strains. Intraduodenal infusion of HCI and a liquid meal significantly increased bicarbonate secretion in both strains; however, the responses were much less in OLETF than LETO rats. In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants.

Role of Gastric Juice in Feedback Regulation of Rat Pancreatic Secretion by Luminal Proteases

The role of gastric juice in the intestine on the pancreatic secretory response to intraduodenal infusion of trypsin inhibitors or to diversion of bile and pancreatic juice from the intestine was studied in conscious rats with pylorus ligation and gastric juice drainage. In absence of gastric juice in the intestine, diversion of bile and pancreatic juice from the intestine stimulated pancreatic secretion, but the incremental protein and fluid secretory responses to diversion of bile and pancreatic juice were increased approximately 2.9-fold and 2.5-fold, respectively, by intraduodenal infusion of HCl (60 microEq/h). Intraduodenal infusion of HCl (240 microEq/h) had no effect on the pancreatic secretory response to infusion of lima bean trypsin inhibitor (20 mg). These results support the hypothesis that the inhibitory effect of atropine on the pancreatic secretory response to diversion of pancreatic juice or bile and pancreatic juice is secondary to inhibition of gastric acid secretion. The lack of effect of HCl on the pancreatic response to trypsin inhibitor contradicts the hypothesis that acid in the intestine is important or necessary for the feedback response to loss of intraluminal protease activity. It is proposed that acid in the intestine augments the pancreatic response to diversion of pancreatic juice or bile and pancreatic juice by reducing intraluminal pH and thereby inactivating residual pancreatic proteases.

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

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 X kg-1 X h-1), but decreased during infusion of 4 U X kg-1 X 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 affect 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 X kg-1 X 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.

Impaired secretin release in chronic alcoholic dogs.

Plasma immunoreactive secretin has been compared before and after stimulation by intraduodenal infusion of HCl in 3 dogs who had received 2 g-kg-1-day-1 alcohol for 3 years and 4 non-alcoholic control dogs. After HCl infusion, blood secretin was lower in chronic alcoholic animals than in controls. This decreased post-stimulation concentration of secretin in chronic alcoholic dogs was in contrast to the increased release of gastrin after a meal which has been previously described.

Effect of nicotine on serum secretin and exocrine pancreatic secretion

The effect of nicotine (100 mug/kg hr-1) on serum secretin and pancreatic secretions was studied in dogs with chronic pancreatic fistulas. Release of immunoreactive secretin (IRS) was stimulated by intraduodenal infusion of HCl (9.6 mEq/30 min). Pancreatic flow rate and bicarbonate and protein secretions were stimulated either by intestinal acidification or infusion of exogenous secretin (1.0 IU/kg hr-1). It was found that nicotine delayed the appearance of peak IRS concentrations in response to intraduodenal HCl by about 20 min. However, nicotine had no effect on the total amount of IRS released nor was this delay accompanied by a similar delay in the appearance of peak bicarbonate output. Furthermore, nicotine did not affect pancreatic secretory function stimulated by either HCl or exogenous secretin. These data do not support the thesis that nicotine plays an important role in the pathogenesis of duodenal ulcers in smokers by inhibiting the pancreatic secretion of bicarbonate.

Pyloric-sphincter studies in peptic-ulcer patients: pylorus in peptic ulcer.

Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17 +/- 0.71) mm Hg) was significantly lower than controls (9.40 +/- 0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30 +/- 1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion of HCl to 15.72 +/- 2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients.

Radioimmunoassay for secretin using Nalpha-tyrosylsecretin and [Tyr1]-secretin.

Sensitive radioimmunoassay for secretin was developed by using synthetic preparation of porcine secretin and its related analogs. The secretin-specific antisera with titers ranging 1: 20,000-1 : 150,000 were generated in rabbits against highly purified synthetic secretin. The labeled antigen was prepared by radioiodinating by the chloramine-T method synthetic secretin analog, Nalpha-tyrosylsecretin or [Tyr1]-secretin, both of which were proved to have almost identical immunoreactivities with that of secretin itself. The immunoassay was performed by the double-antibody method using synthetic secretin as standard. The lowest detectable amount of secretin in the present assays was 5-10pg/tube. Human duodenum extract with hot water contained secretin or secretin-like material that shows a parallel displacement curve to the standard in the immunoassay system used. Serum levels of secretin immunoreactivity in man rose up to 250 pg/ml by intraduodenal infusion of HCl and to 800-1,000 pg/ml by i.v. injection of 1 cu/kg of Boots natural secretin.

Effects of intraduodenal administration of HCl and glucose on circulating immunoreactive secretin and insulin concentrations.

A new radioimmunoassay for secretin was used to investigate (a) serum secretin responses to intraduodenally infused HCl and glucose, (b) the metabolic half-life and the volume of distribution of exogenous secretin and (c) the effect of endogenously released secretin on insulin secretion in 25 anesthetized dogs. Portal and femoral venous blood samples were taken simultaneously before, during, and after intraduodenal infusion of HCl (21 meq/30 min) and glucose (131 ml/30 min). Control experiments were performed with intraduodenal infusion of saline. Mean portal venous immunoreactive secretin concentration of six dogs rose from 313 muU/ml before to 1,060 muU/ml 10 min after initiation of the intestinal acidification (P < 0.005). Femoral venous immunoreactive secretin concentration rose from 220 muU/ml before to 567 muU/ml 15 min after intestinal acidification (P < 0.01). Secretin concentrations remained elevated during the remainder of the infusion. In the same six dogs mean portal venous immunoreactive insulin concentration rose from 38 muU/ml before to 62 muU/ml at the end of the infusion (P < 0.05). Peripheral immunoreactive insulin, glucose, and free fatty acid concentrations, however, did not change significantly. Pancreatic exocrine function was studied in four dogs. The rise in secretin concentration was followed promptly by a highly significant increase in exocrine pancreatic flow rate and bicarbonate secretion, indicating biological activity of the circulating immunoreactive secretin. The effect of intraduodenal infusion of glucose on immunoreactive secretin concentration was studied in 12 dogs. Glucose in concentrations ranging from 2.5% to 10% had no detectable influence on portal or peripheral secretin concentration. Infusion of 50% glucose caused a slight decline in secretin concentration. The metabolic clearance rate, half-life of disappearance, and volume of distribution of exogenous secretin was studied in three dogs by the constant infusion technic. The metabolic clearance rate was 730+/-34 ml/min, volume of distribution was 17.4+/-0.8% of body weight, and the half-life of disappearance was 2.8+/-0.1 min. It could be calculated that 1.38 U/kg-h(-1) of endogenous secretin was released into the peripheral circulation during the steady state period of the HCl infusion experiments. The data indicated that immunoreactive secretin was released rapidly after intestinal acidification, continued to be secreted throughout the duration of HCl infusion, and was promptly distributed in the extracellular compartment. Furthermore, they suggested that endogenously released secretin could stimulate insulin secretion. The HCl-mediated insulinogenic effect of immunoreactive secretin, however, was too weak to influence peripheral immunoreactive insulin, glucose, and free fatty acid concentrations. The failure of intraduodenal glucose to stimulate secretin release suggests that secretin is not the insulin-stimulatory factor released from the gastrointestinal tract in response to glucose.

Effect of phenformin on the exocrine function of the pancreas and on insulin secretion after intraduodenal infusion of HCL and intravenous injection of secretin.

The effect of phenformin on the exocrine function of the pancreas was studied in thirteen healthy subjects. Pancreatic exocrine secretion was stimulated by intraduodenal infusion of 100 ml. of a 0.1 N hydrochloric acid solution and, after fifty minutes, intravenous injection of 1 U. secretin per kilogram of body weight. At the same time serum insulin level was determined by a radioimmunologic method. In each subject the test was performed twice; the first test provided control values, and the second was preceded by treatment with phenformin. Administration of the antidiabetic biguanide markedly reduced the basal secretion rate and its amylase content and also inhibited the increase in secretion normally caused by either intraduodenal infusion of a HCI solution or injection of secretin. In these healthy subjects, intraduodenal infusion of a HCI solution produced a smaller increase in insulin secretion than did intravenous injection of secretin. Previous phenformin treatment largely eliminated the increase in insulinemia after intraduodenal infusion of a HCI solution, whereas it failed to affect the increase in insulinemia after secretin injection. The clinical significance of these observations is discussed.

Pancreatic Secretion in the Sheep

SUMMARY Evidence is presented that: (1) Pancreatic secretion in the sheep is continuous, even during fasting and after the reticulo-rumen has been emptied. (2) There is normally no response to feeding, although a response can be elicited after a prolonged fast. (3) The pancreas responds by an increased output of fluid and enzymes to pilocarpine, vagal stimulation (direct, and by insulin hypoglycaemia), secretion, intraduodenal infusion of HCl and to the addition of acetic acid to the rumen contents. (4) The output of fluid, bicarbonate, amylase, protease and lipase is very low when compared with the dog. This evidence is interpreted to show that: (a) The pancreas is capable of a low level of secretion in the absence of stimuli. (b) Although the gland can be stimulated by both humoral and nervous pathways, maintenance of the normal rate of secretion depends mainly on humoral stimuli released from the intestine. (c) The action of acetic acid is mediated by its stimulatory action on HCL output by the abomasum.