Both upper and lower (the most distal 1 to 2 cm) esophageal sphincters were demonstrated manometrically in 10 adult male and female opossums. A variety of agonists were used to seek differences between circular muscle from the sphincteric segment and more rostral levels, recording in vitro the isometric contractions of strips from the distal 6 cm. Significant differences in threshold concentration occurred for acetylcholine (4 animals), carbachol (3), methacholine (3), nicotine (3), DMPP (1, 1-dimethyl4-phenylpiperazinium iodide) (3), norepinephrine (4), norepinephrine with propranolol (4); the more distal strips being more sensitive. The gradient of threshold was much steeper for norepinephrine than for the other drugs. Maximal responses did not differ among levels for the choline esters or ganglionic stimulants, but showed proximal diminution for norepinephrine. Responses among the 6 levels of the esophagus were identical (or showed only small differences) when using barium (3 animals), atropine (3), and potassium (3). The sphincter is defined, at least in part, in the esophageal wall rather than in the central nervous system. The greater magnitude

of the difference in sensitivity to norepinephrine than for the other agents suggests that the adresergic innervation is important in defining the lower esophageal sphincter.

The decapeptide caerulein was tested in the dog for activity on the biliary system with a radiographic technique using foglycamic acid as a contrast medium. The threshold doses of caerulein for cholecystokinetic activity by 1.v. and s. c. routes were 0.001 and 0.01 g/kg resp and spasmogenic effects on the gallbladder with high doses (1 ug/kg) lasted up to 6 to 7 hr. The effect of caerulein on the intra- and extrahepatic bile ducts was documented by the roentgenographic disappearance of these ducts and the spasmogenic activity of caerulein appeared to spare the intraduodenal portion of the choledochus. The observed action of caerulein resembles that of the endogenous hormone cholecystokinin-pancreozymia.

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Effects of 2-phenyl-2-(2-pyridyl)-thioacetamide (antigastrin) on gastric acid secretion was studied in 4 dogs with Heidenhain pouches and isolated innervated antrums and 5 dogs with Heidenhain pouches and gastric fistulas. Antigastrin significantly inhibited fundic pouch gastrin secretion with maximal inhibition ranging from 45.2 ± 11% with 10 mg dose to 93.9 ± 1.9% for 160 mg dose of antigastrin. Duration of maximum inhibition was less than 60 min with 10 and 20 mg; 40 mg or greater caused sustained inhibition for 120 to 180 min. In gastric fistula dogs, antigastrin was less effective in inhibiting gastric secretion stimulated by 2-deoxy-D-glucose and histamine; 80 mg of antigastrin significantly inhibited response to 2-deoxy-D-glucose by 40% while 160 mg produced retching. In gastric fistula and denervated fundic pouch dogs, histamine-induced gastric acid secretion was inhibited by antigastrin (40 mg) by 43% and 46% resp. The precise role and specificity of antigastrin in inhibition of nervousor histamine-stimulated gastric secretion is unclear; interference with histamine- and vagally stimulated gastric juice may seemingly represent inhibition of potentiating background gastrin.

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The effect of cholecystokinin-pancreozymin on pepsin secretion stimulated by the cholinomimetic agent acetyl-6-methylcholine (mecholyl) was studied in six adult mongrel dogs, each with a vagally denervated Heidenhain pouch. Cholecystokinin-pancreozymin (1.0 Ivy dog unit per min i.v.) produced a significant inhibition of gastric pepsin secretion stimulated by mecholyl (2 ug/min). Pepsin inhibition was prompt and was 41% complete within 10 min of the start of cholecystokinin-pancreozymin administration, and 85% complete after 60 min. Pepsin secretion was reduced by cholecystokinin-pancreozymin from a mecholylstimulated high value of about 100 mg tyrosine per 10 min to a resting value of nearly 25 mg tyrosine per 10 min. Cholecystokinin-pancreozymin significantly inhibits the acid response to gastrin extract, to synthetic peptidase and to endogenously released gastrin and seemingly may be enterogastrone.

The minimum amount of 2-deoxy-D-glucose given as a single rapid i.v. injection which would invariably cause a sustained secretion of gastric acid in normoglycemic rats was 25 mg, with the delay in onset (3 to 30 min) being significantly correlated to plasma glucose (delay was longest when the plasma glucose concentration was highest). If the initial plasma glucose concentration was greater than 200 mg/100 ml, this dose of 2-deoxy-D-glucose did not cause an increase in gastric acid output. An established secretion of gastric acid resulting from the administration of 2-deoxy-D-glucose could always be ended by the 1.v. infusion of high levels of glucose. A preliminary dose of 90 mg of 3-0methylglucose prevents the gastric secretory response that should follow injection of 25 mg of 2-deoxyD-glucose; however, a further dose of 3-0-methylglucose is followed by the typical increase in gastric acid output. Since both glucose and 3-0-methylglucose can prevent 2-deoxy-D-glucose from exciting the gastric secretory center in the brain it appears that the same transport system is used. The use of 2-deoxy-D-glucose for purposes of investigation in man is hazardous because the characteristics of the blood-brain barrier are such that the cells of the brain become progressively more accessible to 2-deoxyD-glucose as the plasma glucose concentration falls below normal, and the effects of 2-deoxy-D-glucose can be reversed only slowly.

Gastric secretion in response to i.v. infusions of histamine and pentagastrin, alone and in combination, was studied in 4 men and in dogs. In man, mean acid outputs stimulated by combinations of histamine and pentagastrin, in doses (0.04 mg/kg/hr and 6.0 μg/kg/ hr, resp.) that produced maximal responses when given alone, were not significantly higher than the maxdmal observed response to either agent alone and clearly were below the calculated maximal response to histamine. This combination of stimulants did not potentiate pepsin secretion either. In dogs with gastric fistulas, equivalent combinations of histamine and pentagastrin potentiated gastric acid

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Pancreatic secretion volume (ml/min), pancreatic blood flow (ml/min), cardiac output (ml/min/kg) and pancreatic perfusion rate (ml/min/100g) were measured in control dogs and dogs infused with secretin, pancreozymin, urecholine or pentagastrin. The values for secretion volume, blood flow, cardiac output and perfusion rate were 0.012, 15.6, 182 and 57, resp., in control dogs and 0.465, 45.8, 240 and 164.2, resp., in response to secretin infusion. Secretion volume, blood flow and perfusion rate were increased by infusion of pancreozymin, urecholine and pentagastrin but to a lesser extent than the increase produced by infusion of secretin. Secretin also increased total blood and perfusion rate to esophagus, stomach, duodenum, gallbladder, pancreas, jejunum, ileum and colon.

The pancreas of male Sprague-Dawley rats fed a raw soybean supplement (with its naturally occurring heat-labile trypsin inhibitor) was 20 to 40% larger than the pancreas of a control group fed a heated soybean-supplemented diet. Both the specific activity and content of amylase were markedly increased in the pancreas of rats fed a daily supplement of purified trypsin inhibitor from soybean (0.6% w/w), ovomucoid (0.6% w/w) and bovine pancreas (0.043% w/w). Right or left vagotomy did not influence the response of the pancreas to raw soybean-supplemented diet and purified trypsin inhibitor. The primary function of the endogenously secreted pancreatic trypsin inhibitor may be to potentiate enzyme synthesis by the acinar cell thus providing an important stimulus for the repletion of digestive enzymes.

3154 EFFECT OF PRESSURE ON THE INTEGRITY OF THE DUCT-ACINAR SYSTEM OF THE PANCREAS. (E.) Pirola, R. C. (Roy. Free Hosp., London, England) and A. E. Davis. Gut 11(1):69-73, 1970.

Tests using India ink introduced into the pancreatic ducts of adult cats show that even in a 15-min period the duct contents can largely escape into the interstitial tissues at pressures below the maxiumum secretory pressure of the pancreas. There was a close correlation between the pressure in the pancreatic duct and the amount of ink seen in the inter

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stitial tissues, and the escape of ink (which appears to leave through clefts between the acinar cells) was only obvious at pressures of 30 and 40 mm Hg. Stimulated secretory pressure rose from 12 to 15 m Hg during the control period to peaks of about 47 mm Hg within 10 min. Apart from pressure, other factors such as pancreatitis and the nature of the duct contents, can affect the integrity of the duct-acinar system.

3155 THE GASTROINTESTINAL STUMULUS TO INSULIN RELEASE: II. A DUAL ACTION OF SECRETIN. (E.) Kraegen, E. W. (St. Vincent's Hosp., Darlinghurst, New South Wales, Australia), D. J. Chisolm, J. D. Young and L. Lazarus. J Clin Invest 49(3): 524-529, 1970.

To further study the role of secretin in insulin release in normal subjects, 2 consecutive 20 min 1.v. glucose infusions were administered to 9 healthy male volunteers (aged 18-23 yr) 150 min apart with and without intervening secretin infusion (10 U) given to approximate serum secretin levels seen after oral glucose ingestion. A highly significant potentiation of the insulin response to the postsecretin glucose infusion occurred when secretin was given 7 or 25 min before glucose (in the latter case, serum secretin was undetectable during the glucose infusion). Despite the augmented insulin response, no consistent change in blood glucose variation was observed and this is consistent with the suggestion that the facilitated disposal of an alimentary glucose load is not dependent solely on enhanced insulin secretion.

were studied in 7 healthy human subjects during continuous i.v. infusion of secretin (3 U/kg/hr) and pancreozymin (1 U/kg/hr). Glucagon significantly depressed pancreatic secretory flow (without an accompanying reduction in bicarbonate levels) and total protein concentration in all subjects, as maximal inhibition of hormonally stimulated volume and protein concentration always occurred within the first 5 to 10 min and the inhibitory effect lasted no longer than 5 to 20 min for volume and 10 to 30 min for protein concentration. Changes in blood glucose concentration before and after glucagon administration did not follow a consistent pattern and bore no apparent relation to changes in pancreatic secretory volume. Glucagon may have a regulatory role in the control of pancreatic secre