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Localization of the Mechanism for Inhibition of Gastric Secretion by Acid in Intestine
Vol. 49, No.1 Printed in U.S.A .
GASTROENTEROLOGY
Copyright © 1965 by The Williams & Wilkins Co.
LOCALIZATION OF THE MECHANISM FOR INHIBITION OF GASTRIC SECRETION BY ACID IN INTESTINE STANISLAW KONTUREK, M.D. AND MORTON
I.
GROSSMAN, ~-J.D.
Veterans Administration Center and School of Medicine, University of California, Los Angeles, California
Inhibition of gastric secretion by duodenal acidification is a well known phenomenon. 1• 3 It is however still uncertain which parts of the intestine may be involved in this inhibitory mechanism. Andersson and Uvnas have shown2 that the effect can be elicited from the isolated duodenal bulb but the effectiveness of other levels of the intestine has not been systematically tested. The present study was designed to determine the role of different parts of the duodenum in inhibition of gastric secretion by endogenous duodenal acidification and to establish how much of the small intestine had to be removed or bypassed to abolish this effect.
and a small portion of proximal jejunum to a point just beyond the ligament of Treitz. After the first three stages gastrointestinal continuity was reestablished by end-to-end gastroduodenostomy or duodenoduodenostomy. After excision of the distal portion of the duodenum, end-to-side gastrojejunostomy was performed. All secretory tests were repeated 10 to 14 days after recovery from each of these procedures. The animals were fasted for at least 18 hr before each test and were used not more than three times per week. Throughout each test 0.15 M sodium chloride solution was infused intravenously at a rate of 30 ml per hr by a peristaltic pump. The basal output from the Heidenhain pouches was collected for 15 min and then gastrin was added to the saline being infused to give a dose rate of 10 g per hr (expressed as equivalent wet weight of mucosa). Gastrin ·was prepared from hog antral mucosa according to a method previously described. 7 Several batches of extract were combined to give a pool of sufficient size for the entire study. Gastric juice was collected every 15 min. Volume was measured and titratable acidity (end point pH 7.0) 'vas determined with an autoburet titrator and pH-meter, using 0.2 N N aOH. The results are expressed in J.Leq HCl secreted per 15 min. In one series of tests the response of the Heidenhain pouch to gastrin was studied with the gastric fistula closed for the initial 90 min, open for 60 min, and then closed for a further 90 min. In another group of experiments the gastric fistula was initially open for 90 min, closed for 60 min and then open again for an additional 90 min. In this way the gastric fistula was alternately closed and open during the same experiment, so that acid produced by the main stomach was either drained to the exterior
Method Two mongrel dogs (body weight 14 and 17 kg) were prepared with both a Heidenhain pouch and a Thomas cannula in the main stomach to form a gastric fistula. After completing control tests the dogs underwent the following procedures: I. excision of the pyloric sphincter; II. transplantation at the middle portion of the duodenum, containing the biliary and pancreatic ducts, as a diverticulum into the jejunum 10 em distal to the ligament of Treitz; III. excision of the duodenal bulb (that portion between the pylorus and the entry of the bile duct); and IV. excision of the remaining distal portion of the duodenum Received February 23, 1965. Accepted March 16, 1965. Address requests for reprints to : Dr. M. I. Grossman, VA Center, Los Angeles, Calif. 90073. This study was supported in part by United States Public Health Service Grant No . AM08354 from the National Institute of Arthritis and Metabolic Diseases. We are grateful to John Washington for expert technical assistance.
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INHIBITION OF GASTRIC SECRETION
(gastric fistula open) or passed into the intestine (gastric fistula closed). In those experiments in which the gastric fistula was initially closed, the secretion obtained from the main stomach immediately after opening the gastric fistula was discarded; its volume was usually neglible and it never exceeded the volume secreted in any subsequent 15-min period. Percentage of inhibition of acid output fmm the Heidenhain pouch caused by closing or percentage of increase caused by opening the gastric fistula was calculated for each test. The mean output of acid from the Heidenhain pouches during the three 15-min periods immediately preceding the opening or closing of the gastric fistula was taken as control or 100 % and was compared to the mean output of the pouches during the four 15-min periods immediately following opening or closing the gastric fistula. Significance of differences of mean per TABLE
75
cent inhibition or stimulation was determined by the "t" test for unpaired values. Results
A. The Effect of Opening and Closing the Gastric Fistula on Acid Secretion from Heidenhain Pouches
In the experiments with duodenum intact and with gastric fistula initially closed, the response of the Heidenhain pouches to gastrin reached a plateau during this initial phase. Opening the gastric fistula caused a significant rise in acid secretion by the pouch (table 1). When the gastric fistula was closed again for an additional 90-min acid output from the pouch gradually declined to about half of the initial plateau (fig. 1). In the other series of experiments with the gastric fistula initially open, the secretory response from the Heidenhain pouch
1. Acid secretion jTom the H eidenhain pottch (H P) under basxl conditions and in response to gastrin (10 g per hr ) in dogs with gastric fistula (GF) open or closed after different procedures Acid response of HP to gastrin Procedure
Basal secretioJ from HP
Tests with GF closed, th en open Controla
J.L tQ /
15 min
Dodeunum intact
0
Exci sion of pyloric sphincter (I)
0
Increaseb
Acid response of GF to gastrin
Tests with GF open, then closed Control'
Inhibitiond
Tests with GF closed, then open
T ests with GF open, then closed
p.eq/ 15 min p.eq/min 15 p.eq/ 15 min % % p.eq/15 min 134 ± 25 79.0 ± 4 . 6 181 ± 19 62.6 ± 4.5 2822 ± 149 2828 ± 183 (6) (6)' p < 0.01 p < 0.01
189 ± 33 82.0 ± 5.2 299 ± 19 50.3 ± 4.0 2881 ± 113 2577 ± 123 (6) p < 0.01 (6 ) p < 0.01
Transplantation of midportion (II)
30 ± 11 364 ± 43 68.4 ± 17.7 365 ± 56 68.0 ± 4.7 4641 ± 337 4070 ± 422 (6) (6) p < 0.01 p < 0 .01
Excision of bulb
56 ± 31 553 ± 31 57 . 1 ± 24 .5 832 ±56 48.4 ± 12.7 5636 ± 108 7547 ± 250 (4 ) p < 0.05 (4) p < 0.01
(III)
Excision of distal part (IV)
100 ± 22 857 ± 89 3.4 ± 12.0 987 ± 60 7.5 ± 7.9 5730 ± 134 6570 ± 359 (4 ) p > 0.1 (4) p > 0.1
Control is mean value for the three peri ods preceding opening the gastric fistula. Increase percentage is mea n per cent rise during four 15-min periods following opening t he gastric fistula, compared with control. c Control is mean va lue for last three periods before closing gastric fist ul a. a Inhibition percentage is mea n per cent decrease during four 15-min periods following closing the gastric fistula, compared with control. 'Values are mean± standard error. Figures in parentheses indica te tota l number of tests; the two dogs had an equal number of tests. a
b
76
KONTUREK AND GROSSMAN
Vol. 49, No . 1
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Fw. 1. Acid secretion from the Heidenhain pouch in response to gastrin expressed as the percentage of t he control level (mean rate of acid secretion from the fifth, sixth, and seventh 15-min periods after starting gastrin infusion) in dogs with gastric fistula open or closed after different procedures; C = duodenum intact, I = excision of the pyloric sphincter, II = transplantation of the middle portion of the duodenum with biliary and pancreatic ducts into the jejunum as a diverticulum, III = excision of the duodenal bulb, and IV = excision of the distal portion of the duodenum.
declined when acid from the main stomach was diverted into the intestine (table 1). Excision of the pyloric sphincter (procedure I). Although this procedure increased the control responses of the Heidenhain pouches to gastrin by 45 % when compared to the responses when the pyloric sphincter was intact, opening or closing of the gastric fistula produced changes in secretion from the pouch that were of the same direction and size as observed in experiments with the pyloric sphincter intact (table 1). Transplantation of the middle portion of the duodenum with biliary and pancreatic ducts into the jejunum as a diverticulum (procedure I I). This caused a slight increase in the basal secretion of the pouch and a further increase in the response to gastrin to about 170 % above the control level (table 1). However, there was no alteration in the direction or percentage change in the pouch response to opening or closing the gastric fistula (fig. 1). Excision of the duodenal bulb (procedure III). This was followed by a further rise of
the acid secretion from the Heidenhain pouch both under basal conditions and with gastrin stimulation (table 1). Again the diversion of secretion from the main stomach by opening or closing of the gastric fistula caused the same direction and magnitude of changes in the rate of acid secretion by the Heidenhain pouch (table 1, fig. 1). Excision of the distal portion of the duodenum (procedure I V). After this final procedure the mean basal rate of secretion from the Heidenhain pouches was still further increased as \\'aS the control response to gastrin (table 1) . However, the secretion from the pouches was not significantly changed by opening or closing the gastric fistula (table 1, fig. 1). Furthermore, it is of interest that the response of the Heidenhain pouch to gastrin did not show the gradual decline during the last 90 min of the tests as had occurred in all of the previous stages of these studies.
July 1965
I N HIBITION OF GASTRIC SECRETION
B. Secretion of H Clfrom the Main Stomach in R esponse to Gastrin
Excision of the pyloric sphincter did not change the rate of secretion of HCl from the main stomach in response to gastrin in comparison with the control levels. After transplanting the middle portion of the duodenum to the jejunum, the mean rate of acid secretion rose by 62 % over the control level (table 1). A further increase in acid secretion to about 100 % above the control level occurred with excision of the duodenal bulb but no further change was seen when the remainder of the duodenum was resected. Discussion
Two striking observations emerge from this study. First, progressive removal or exclusion of portions of the duodenum led to progressive increases in the rate of acid secretion. Second, it was necessary to remove or exclude the entire duodenum before inhibition of acid secretion by intestinal acidification could be eliminated; it would appear that only the duodenum is a receptor site for inhibition of gastric secretion by acidification and that all portions of it are responsive to this action of acid. It is clear that there is a difference in the effect on acid secretion between the short t erm absence of duodenal acidification (diverting juice from the main stomach to the exterior for 90 min) and long t erm absence of duodenal acidification (excision or exclusion of portions of the duodenum). The latter effect is very much larger than the former. Thus, diversion of acid away from the duodenum on a short term basis led to doubling of secretion from the Heidenhain pouch whereas excision or exclusion of the entire duodenum resulted in a sixfold increase. The long term effect of excision and exclusion had apparently plateaued by 2 weeks after each procedure because there was no tendency for progressive increase during the successive tests of any one phase of the study. The long t erm effect of shielding the duodenum from the acid was observed in both the basal and gastrin-stimulated secretion from the H eidenhain pouch. There was
77
also an increase in gastrin-stimulated secretion from the main stomach (two- to t hreefold) but this was proportionately smaller than in the pouch (six- to sevenfold) . Whether this long term effect is caused by prolonged absence of acid from the duodenum or whether it requires duodenal resection cannot be fully determined from our studies, but the previous studies of Andersson et al. 5 and the results of procedure II in the present study suggest that prolonged absence of acid is at least in part responsible. In any case, it would appear that the duodenal mucosa exerts a chronic inhibitory action on the acid-secreting glands and that this can be released by a variety of means. Our study confirms the investigations of Brockney et al.,4 who observed an increase in 24-hr output of HCl by H eidenhain pouches after complete removal of the duodenum and upper part of the jejunum. Quintana et al. 6, also using 24-hr collections, also found t hat resection of the duodenum and transplantation of the biliary and pancreatic ducts to the ileum evoked an increase in secretion from denervated pouches. Diversion of bile and pancreatic juice into the distal intestine has been shown to be associated with increased secretion from Heidenhain pouches. Since this procedure is usually accomplished by moving various amounts of duodenal mucosa along with the ducts, the effect of duct diversion alone will have to be more critically studied. Summary
In dogs with both H eidenhain pouch and gastric fi stula, gastrin (10 g per hr) was given continuously intravenously. Pouch secretion increased when the gastric fistula was opened, diverting acid from the main stomach to the exterior, and decreased when the gastric fistula was closed, allowing acid from the main stomach to enter the intestine. T ests were repeated after the following procedures: (I ) excision of the pyloric sphincter ; (II) transplantation of the midportion of the duodenum, containing the bile and pancreatic ducts, to the jejunum as a diverticulum; (III) exCiswn of the duodenal bulb; and (IV) removal of the
78
KONTUREK AND GROSSMAN
remaining duodenum. Each procedure was followed by an increase in pouch secretion both under basal conditions and in response to gastrin. However, only complete excision of the entire duodenum abolished the inhibitory effect of intestinal ecidification. Apparently the mechanism for inhibition of gastric secretion by intestinal acidification is confined to the duodenum. REFERENCES 1. Andersson , S. 1960. Inhibitory effects of hydrochloric acid in duodenum on gastrin stimulated gastric secretion in H eidenhain pouch dogs. Acta Physiol. Scand. 50: 105. 2. Andersson, S., and B. Uvniis. 1961. Inhibition of postprandial gastric secretion in Pavlov pouches by instillation of hydrochloric acid into the duodenal bulb. Gastroenterology 41: 486.
Vol. 49, No.1
3. Wormsley, K. G., and M. I. Grossman. 1964. Inhibition of gastric acid secretion by secretin and by endogenous acid in the duodenum. Gastroenterology 47: 72. 4. Brockney, E. L., A. P. T hai, and 0. H. Wangensteen. 1955. R ole of du ode num in control of gastric secretion. Proc. Soc. Exp. Bioi. Med. 88: 302. 5. Andersson, S., C. Elwin, and B. Uvniis. 1958. The effect of exclusion of the antrum and duodenum, and subsequent resection of the antrum, on t he acid secretion in Pavlov pouch dogs. Gastroenterology 34: 636. 6. Quintana, R ., S. Kohatzu, E . R. Woodward, and L. R. Dragstedt. 1964. Mechanism of duodena l inhibition of gastric secrtion. Arch. Surg. 89: 585. 7. Gillespie, I. E., and M . I. Grossman. 1963. Inhibition of gas tric secretion by extracts cont aining gastrin. Gastroenterology 44: 301.
GASTROENTEROLOGY
Copyright © 1965 by The Williams & Wilkins Co.
LOCALIZATION OF THE MECHANISM FOR INHIBITION OF GASTRIC SECRETION BY ACID IN INTESTINE STANISLAW KONTUREK, M.D. AND MORTON
I.
GROSSMAN, ~-J.D.
Veterans Administration Center and School of Medicine, University of California, Los Angeles, California
Inhibition of gastric secretion by duodenal acidification is a well known phenomenon. 1• 3 It is however still uncertain which parts of the intestine may be involved in this inhibitory mechanism. Andersson and Uvnas have shown2 that the effect can be elicited from the isolated duodenal bulb but the effectiveness of other levels of the intestine has not been systematically tested. The present study was designed to determine the role of different parts of the duodenum in inhibition of gastric secretion by endogenous duodenal acidification and to establish how much of the small intestine had to be removed or bypassed to abolish this effect.
and a small portion of proximal jejunum to a point just beyond the ligament of Treitz. After the first three stages gastrointestinal continuity was reestablished by end-to-end gastroduodenostomy or duodenoduodenostomy. After excision of the distal portion of the duodenum, end-to-side gastrojejunostomy was performed. All secretory tests were repeated 10 to 14 days after recovery from each of these procedures. The animals were fasted for at least 18 hr before each test and were used not more than three times per week. Throughout each test 0.15 M sodium chloride solution was infused intravenously at a rate of 30 ml per hr by a peristaltic pump. The basal output from the Heidenhain pouches was collected for 15 min and then gastrin was added to the saline being infused to give a dose rate of 10 g per hr (expressed as equivalent wet weight of mucosa). Gastrin ·was prepared from hog antral mucosa according to a method previously described. 7 Several batches of extract were combined to give a pool of sufficient size for the entire study. Gastric juice was collected every 15 min. Volume was measured and titratable acidity (end point pH 7.0) 'vas determined with an autoburet titrator and pH-meter, using 0.2 N N aOH. The results are expressed in J.Leq HCl secreted per 15 min. In one series of tests the response of the Heidenhain pouch to gastrin was studied with the gastric fistula closed for the initial 90 min, open for 60 min, and then closed for a further 90 min. In another group of experiments the gastric fistula was initially open for 90 min, closed for 60 min and then open again for an additional 90 min. In this way the gastric fistula was alternately closed and open during the same experiment, so that acid produced by the main stomach was either drained to the exterior
Method Two mongrel dogs (body weight 14 and 17 kg) were prepared with both a Heidenhain pouch and a Thomas cannula in the main stomach to form a gastric fistula. After completing control tests the dogs underwent the following procedures: I. excision of the pyloric sphincter; II. transplantation at the middle portion of the duodenum, containing the biliary and pancreatic ducts, as a diverticulum into the jejunum 10 em distal to the ligament of Treitz; III. excision of the duodenal bulb (that portion between the pylorus and the entry of the bile duct); and IV. excision of the remaining distal portion of the duodenum Received February 23, 1965. Accepted March 16, 1965. Address requests for reprints to : Dr. M. I. Grossman, VA Center, Los Angeles, Calif. 90073. This study was supported in part by United States Public Health Service Grant No . AM08354 from the National Institute of Arthritis and Metabolic Diseases. We are grateful to John Washington for expert technical assistance.
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July 1965
INHIBITION OF GASTRIC SECRETION
(gastric fistula open) or passed into the intestine (gastric fistula closed). In those experiments in which the gastric fistula was initially closed, the secretion obtained from the main stomach immediately after opening the gastric fistula was discarded; its volume was usually neglible and it never exceeded the volume secreted in any subsequent 15-min period. Percentage of inhibition of acid output fmm the Heidenhain pouch caused by closing or percentage of increase caused by opening the gastric fistula was calculated for each test. The mean output of acid from the Heidenhain pouches during the three 15-min periods immediately preceding the opening or closing of the gastric fistula was taken as control or 100 % and was compared to the mean output of the pouches during the four 15-min periods immediately following opening or closing the gastric fistula. Significance of differences of mean per TABLE
75
cent inhibition or stimulation was determined by the "t" test for unpaired values. Results
A. The Effect of Opening and Closing the Gastric Fistula on Acid Secretion from Heidenhain Pouches
In the experiments with duodenum intact and with gastric fistula initially closed, the response of the Heidenhain pouches to gastrin reached a plateau during this initial phase. Opening the gastric fistula caused a significant rise in acid secretion by the pouch (table 1). When the gastric fistula was closed again for an additional 90-min acid output from the pouch gradually declined to about half of the initial plateau (fig. 1). In the other series of experiments with the gastric fistula initially open, the secretory response from the Heidenhain pouch
1. Acid secretion jTom the H eidenhain pottch (H P) under basxl conditions and in response to gastrin (10 g per hr ) in dogs with gastric fistula (GF) open or closed after different procedures Acid response of HP to gastrin Procedure
Basal secretioJ from HP
Tests with GF closed, th en open Controla
J.L tQ /
15 min
Dodeunum intact
0
Exci sion of pyloric sphincter (I)
0
Increaseb
Acid response of GF to gastrin
Tests with GF open, then closed Control'
Inhibitiond
Tests with GF closed, then open
T ests with GF open, then closed
p.eq/ 15 min p.eq/min 15 p.eq/ 15 min % % p.eq/15 min 134 ± 25 79.0 ± 4 . 6 181 ± 19 62.6 ± 4.5 2822 ± 149 2828 ± 183 (6) (6)' p < 0.01 p < 0.01
189 ± 33 82.0 ± 5.2 299 ± 19 50.3 ± 4.0 2881 ± 113 2577 ± 123 (6) p < 0.01 (6 ) p < 0.01
Transplantation of midportion (II)
30 ± 11 364 ± 43 68.4 ± 17.7 365 ± 56 68.0 ± 4.7 4641 ± 337 4070 ± 422 (6) (6) p < 0.01 p < 0 .01
Excision of bulb
56 ± 31 553 ± 31 57 . 1 ± 24 .5 832 ±56 48.4 ± 12.7 5636 ± 108 7547 ± 250 (4 ) p < 0.05 (4) p < 0.01
(III)
Excision of distal part (IV)
100 ± 22 857 ± 89 3.4 ± 12.0 987 ± 60 7.5 ± 7.9 5730 ± 134 6570 ± 359 (4 ) p > 0.1 (4) p > 0.1
Control is mean value for the three peri ods preceding opening the gastric fistula. Increase percentage is mea n per cent rise during four 15-min periods following opening t he gastric fistula, compared with control. c Control is mean va lue for last three periods before closing gastric fist ul a. a Inhibition percentage is mea n per cent decrease during four 15-min periods following closing the gastric fistula, compared with control. 'Values are mean± standard error. Figures in parentheses indica te tota l number of tests; the two dogs had an equal number of tests. a
b
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Vol. 49, No . 1
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15 MINUTE PERIODS
Fw. 1. Acid secretion from the Heidenhain pouch in response to gastrin expressed as the percentage of t he control level (mean rate of acid secretion from the fifth, sixth, and seventh 15-min periods after starting gastrin infusion) in dogs with gastric fistula open or closed after different procedures; C = duodenum intact, I = excision of the pyloric sphincter, II = transplantation of the middle portion of the duodenum with biliary and pancreatic ducts into the jejunum as a diverticulum, III = excision of the duodenal bulb, and IV = excision of the distal portion of the duodenum.
declined when acid from the main stomach was diverted into the intestine (table 1). Excision of the pyloric sphincter (procedure I). Although this procedure increased the control responses of the Heidenhain pouches to gastrin by 45 % when compared to the responses when the pyloric sphincter was intact, opening or closing of the gastric fistula produced changes in secretion from the pouch that were of the same direction and size as observed in experiments with the pyloric sphincter intact (table 1). Transplantation of the middle portion of the duodenum with biliary and pancreatic ducts into the jejunum as a diverticulum (procedure I I). This caused a slight increase in the basal secretion of the pouch and a further increase in the response to gastrin to about 170 % above the control level (table 1). However, there was no alteration in the direction or percentage change in the pouch response to opening or closing the gastric fistula (fig. 1). Excision of the duodenal bulb (procedure III). This was followed by a further rise of
the acid secretion from the Heidenhain pouch both under basal conditions and with gastrin stimulation (table 1). Again the diversion of secretion from the main stomach by opening or closing of the gastric fistula caused the same direction and magnitude of changes in the rate of acid secretion by the Heidenhain pouch (table 1, fig. 1). Excision of the distal portion of the duodenum (procedure I V). After this final procedure the mean basal rate of secretion from the Heidenhain pouches was still further increased as \\'aS the control response to gastrin (table 1) . However, the secretion from the pouches was not significantly changed by opening or closing the gastric fistula (table 1, fig. 1). Furthermore, it is of interest that the response of the Heidenhain pouch to gastrin did not show the gradual decline during the last 90 min of the tests as had occurred in all of the previous stages of these studies.
July 1965
I N HIBITION OF GASTRIC SECRETION
B. Secretion of H Clfrom the Main Stomach in R esponse to Gastrin
Excision of the pyloric sphincter did not change the rate of secretion of HCl from the main stomach in response to gastrin in comparison with the control levels. After transplanting the middle portion of the duodenum to the jejunum, the mean rate of acid secretion rose by 62 % over the control level (table 1). A further increase in acid secretion to about 100 % above the control level occurred with excision of the duodenal bulb but no further change was seen when the remainder of the duodenum was resected. Discussion
Two striking observations emerge from this study. First, progressive removal or exclusion of portions of the duodenum led to progressive increases in the rate of acid secretion. Second, it was necessary to remove or exclude the entire duodenum before inhibition of acid secretion by intestinal acidification could be eliminated; it would appear that only the duodenum is a receptor site for inhibition of gastric secretion by acidification and that all portions of it are responsive to this action of acid. It is clear that there is a difference in the effect on acid secretion between the short t erm absence of duodenal acidification (diverting juice from the main stomach to the exterior for 90 min) and long t erm absence of duodenal acidification (excision or exclusion of portions of the duodenum). The latter effect is very much larger than the former. Thus, diversion of acid away from the duodenum on a short term basis led to doubling of secretion from the Heidenhain pouch whereas excision or exclusion of the entire duodenum resulted in a sixfold increase. The long term effect of excision and exclusion had apparently plateaued by 2 weeks after each procedure because there was no tendency for progressive increase during the successive tests of any one phase of the study. The long t erm effect of shielding the duodenum from the acid was observed in both the basal and gastrin-stimulated secretion from the H eidenhain pouch. There was
77
also an increase in gastrin-stimulated secretion from the main stomach (two- to t hreefold) but this was proportionately smaller than in the pouch (six- to sevenfold) . Whether this long term effect is caused by prolonged absence of acid from the duodenum or whether it requires duodenal resection cannot be fully determined from our studies, but the previous studies of Andersson et al. 5 and the results of procedure II in the present study suggest that prolonged absence of acid is at least in part responsible. In any case, it would appear that the duodenal mucosa exerts a chronic inhibitory action on the acid-secreting glands and that this can be released by a variety of means. Our study confirms the investigations of Brockney et al.,4 who observed an increase in 24-hr output of HCl by H eidenhain pouches after complete removal of the duodenum and upper part of the jejunum. Quintana et al. 6, also using 24-hr collections, also found t hat resection of the duodenum and transplantation of the biliary and pancreatic ducts to the ileum evoked an increase in secretion from denervated pouches. Diversion of bile and pancreatic juice into the distal intestine has been shown to be associated with increased secretion from Heidenhain pouches. Since this procedure is usually accomplished by moving various amounts of duodenal mucosa along with the ducts, the effect of duct diversion alone will have to be more critically studied. Summary
In dogs with both H eidenhain pouch and gastric fi stula, gastrin (10 g per hr) was given continuously intravenously. Pouch secretion increased when the gastric fistula was opened, diverting acid from the main stomach to the exterior, and decreased when the gastric fistula was closed, allowing acid from the main stomach to enter the intestine. T ests were repeated after the following procedures: (I ) excision of the pyloric sphincter ; (II) transplantation of the midportion of the duodenum, containing the bile and pancreatic ducts, to the jejunum as a diverticulum; (III) exCiswn of the duodenal bulb; and (IV) removal of the
78
KONTUREK AND GROSSMAN
remaining duodenum. Each procedure was followed by an increase in pouch secretion both under basal conditions and in response to gastrin. However, only complete excision of the entire duodenum abolished the inhibitory effect of intestinal ecidification. Apparently the mechanism for inhibition of gastric secretion by intestinal acidification is confined to the duodenum. REFERENCES 1. Andersson , S. 1960. Inhibitory effects of hydrochloric acid in duodenum on gastrin stimulated gastric secretion in H eidenhain pouch dogs. Acta Physiol. Scand. 50: 105. 2. Andersson, S., and B. Uvniis. 1961. Inhibition of postprandial gastric secretion in Pavlov pouches by instillation of hydrochloric acid into the duodenal bulb. Gastroenterology 41: 486.
Vol. 49, No.1
3. Wormsley, K. G., and M. I. Grossman. 1964. Inhibition of gastric acid secretion by secretin and by endogenous acid in the duodenum. Gastroenterology 47: 72. 4. Brockney, E. L., A. P. T hai, and 0. H. Wangensteen. 1955. R ole of du ode num in control of gastric secretion. Proc. Soc. Exp. Bioi. Med. 88: 302. 5. Andersson, S., C. Elwin, and B. Uvniis. 1958. The effect of exclusion of the antrum and duodenum, and subsequent resection of the antrum, on t he acid secretion in Pavlov pouch dogs. Gastroenterology 34: 636. 6. Quintana, R ., S. Kohatzu, E . R. Woodward, and L. R. Dragstedt. 1964. Mechanism of duodena l inhibition of gastric secrtion. Arch. Surg. 89: 585. 7. Gillespie, I. E., and M . I. Grossman. 1963. Inhibition of gas tric secretion by extracts cont aining gastrin. Gastroenterology 44: 301.