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Origin of gastrin in gastric juice
Origin of Gastrin in Gastric Juice
Paul H. Jordan, Jr, MD, Houston, Texas Bianca S. S. C. Yip, MD, Houston, Texas
In an earlier study, the presence of gastrin in the gastric juice of human subjects was reported [I]. Subsequently this material was extracted from the gastric juice of a patient with the Zollinger-Ellison syndrome. When tested in dogs, it was equally as potent as pentagastrin in the stimulation of acid secretion [2]. Later it was demonstrated that exogenous gastrin was cleared from the blood by the fundic mucosa [3]. The present study was designed to determine if endogenous gastrin in gastric juice moved directly into the gastric lumen from the antral gastrin cells or was cleared from the blood by the fundic mucosa. Material and Methods Four dogs weighing approximately 20 kg were prepared with a Heidenhain pouch, an innervated antral pouch separated from the fundus by a mucosal bridge, and a gastric fistula of the vagally innervated portion of the stomach. Gastrointestinal continuity was re-established by gastrojejunostomy. Experiments were begun no earlier than three weeks after operation and the dogs were fasted eighteen hours before each experiment. Individual collections of gastric juice from the gastric fistula and the Heidenhain pouch were made continuously every fifteen minutes throughout each experiment. Secretions from antral pouches in response to betazole hydrochloride were small and therefore were collected as one sample for the duration of an experiment.
From the Surgical Services of the Cora and Webb Mading Department of Surgery, Baylor College of Medicine, and the Veterans Administration Hospital, Houston, Texas. Reprint requests should be addressed to Dr Paul Ii. Jordan, Jr, 1200 Moursund Avenue, Houston, Texas 77025.
336
Before initiating an experiment, fifteen minute basal collections were made. The study was not performed until basal secretion from the gastric fistula was less than 0.05 mEq per fifteen minutes. After basal conditions were obtained, gastric secretion was stimulated either by subcutaneous injection of betazole hydrochloride (Histalog) or by constant perfusion of the antrum with a suspension of liver powder. Each stimulant was used in three experiments in each dog. The volume of each fifteen minute collection of gastric juice was measured and an aliquot was titrated with 0.1 N sodium hydroxide to pH 7.0 using an automatic titrator and pH meter (Radiometer, Copenhagen, Denmark). A sample of peripheral venous blood and an aliquot of each collection of gastric juice were analyzed for gastrin by radioimmunoassay [4]. .Results Liver Perfusion. Perfusion of the antrum with a suspension of liver powder produced an increase in gastric secretion from both the gastric fistulas (Table I) and the Heidenhain pouches (Table II). As the acid secretion increased, the concentration and total amount of gastrin in the gastric juice also increased. Because of the wide variation in the amount of gastric juice produced by the different dogs, comparisons between the amounts of acid and gastrin in the gastric juice were determined for each individual dog by the statistical method of Morrison [5]. Analysis indicated that there was a direct correlation between the amounts of acid and gastrin in the gastric juice from both the gastric fistulas and the Heidenhain pouches, which was statistically significant with p values of CO.01 and <0.05, respectively. Serum gastrin levels increased
The American Journal of Surgery
Origin
TABLE
I
Total Gastrin and Acid Output from Gastric Fistula after Stimulation Perfusion
of Gastrin
of Acid Secretion by
of the Antrum with Liver Suspension Fifteen Minute Collection Periods Control 1
2
1
mEq H+ ng* gastrin
.08 .04
.03 .Ol
.2 .4
2
mEq H+ ng gastrin
.13 .04
.02 .Ol
1.0 .6
3
mEq H+ ng gastrin
.05 .03
.Ol .Ol
.4 .l
4
mEq H+ ng gastrin
.Ol .Ol
.02 .Ol
1
“Geometric Probability
Correlation between Acid and Gastrin output
Liver Perfusion
1.1 2%
2
3
4
2.4 397
4.1 1,374
4.0 1,515
4.2 1,599
3.7 1,936
.957
2,911
1.7 2
1.6 338
2.0 257
2.3 506
1.8 574
2.9 1,411
3.1 930
.806
1.0 21
1.7 276
1.9 106
2.8 204
4.0 621
3.9 527
3.6 541
.937
1.9
1.5 22
1.6 31
1.7 37
2.0 69
1.8 109
.561
.7 14
2.0
38
5
5
6
7
8.
5.9
means”
.872 <.Ol
* Nanogram.
Comments
and reached their peak one hour after perfusion of the antrum was begun. Betazole Stimulation. The results obtained by betazole stimulation were similar to those obtained by perfusion of the antrum with liver. There was a direct correlation between the amounts of acid and gastrin in the gastric juice from the gastric fistulas (Table III) and the Heidenhain pouches (Table IV). The correlation between these two variables from both pouches was statistically significant with a p value of
TABLE II
These studies confirm earlier reports [1-31 that gastrin is present in gastric juice. Numerous investigators reported the presence of histamine in gastric juice on bioassay [6-B], but it was subsequently shown that the amount of histamine in gastric juice is insufficient to be detected by bioassay [9J. The presence of gastrin may provide the explanation for the “histamine equivalent” previously reported in canine gastric juice. The possibility of the presence of gastrin in gastric juice was suggested by Sircus [IO] who found a gastric secretagogue in the gastric juice of two patients with the Zollinger-Ellison syndrome. Since gastrin is the secretagogue found in these tumors, it is reasonable to conclude that gastrin in the gastric juice of these Pouch after Stimulation
of Acid Secretion
by
Fifteen Minute CollectionPeriods
1
2
mEq H+ ng* gastrin
.02 .Ol
-01 .Ol
0 0
.08 .03
.25 30.1
.27 35.5
mEq H+ ng gastrin
0 .Ol
0 .Ol
0 0
.58 .OJ
.82 3.1
.81 24.7
mEq H+ ng gastrin
0
0
0
.Ol
0
0
.05 .02
.04 .05
mEq H+ ng gastrin
.03 .Ol
.03 .Ol
.05 .Ol
.16 .25
.17 .92
Dog 1 2 3 4
“Geometric Probability
means” --__
_
Liver Perfusion
Control 1
2
3
4
5
6
7
.32 11.2
.42 67.0
-67 3.9
.58 122
.73 141
.04 .08
.OJ .05
.04 .07
.18 1.25
.22 1.49
.27 1.83
.39
57.2
8 .40 8.0
Correlation between Acid and Gastrin Output
.746
.80
.346
.13 .17
.08 .31
.713
.35 2.64
.38 6.08
24
.868 .709 <.05
* Nanogram.
Volume 128, September 1974
337
Jordan
and Yip
TotalGastrin
TABLE III
and Acid Output from Gastric Fistula after Stimulation
Acid Secretion
of
with Betazole Fifteen Minute Collection Periods
Dog 1
--.~ mEqH+ ng* gastrin
Correlation between Acid and Gastrin output
Betazole Stimulation
Control .___ 1 2
1 _-__
2
3
4
5
6 -
7
8
.08 .04
.lo .04
1.4 2.0
2.9 733
3.8 1,976
3.5 2,345
2.6 7,967
2.4 1,680
2.7 2,260
2.3 1,702
.443
2
mEq H+ ng gastrin
.ll .02
.04 .Ol
.l .l
.8 44
1.2 247
1.6 489
1.7 374
1.1 127
2.0 208
1.4 a4
.770
3
mEq H+ ng gastrin
.07 .03
.04 .Ol
.5 2.0
1.4 38
2.1 153
1.8 627
2.1 647
2.2 990
2.6 749
2.3 698
.860
4
mEq H+ ng gastrin
.06 .05
.02 .Ol
.l 4.0
.6 59
1.4 349
1.5 187
1.2 108
.9 72
1.0 113
1.9 110
.707
“Geometric
means”
.703 <.05
Probability * Nanogram.
patients initiated the gastric secretory response in rats that constituted a positive bioassay for diagnosis of the Zollinger-Ellison syndrome. The increase in gastrin in the gastric juice after betazole stimulation as well as by chemical stimulation of the antral mucosa suggests, as was previously postulated [I], that betazole is a releaser of gastrin from the antrum. The failure to obtain as great a rise in serum gastrin after antral perfusion with liver or after bet,azole injection in dogs compared with that in human subjects suggests that the fundic mucosa may clear the blood of gastrin more efficiently in the dog than it does in man. McGuigan (II] demonstrated a positive correlation between the gastrin content of the gastric wall and the number of specific immunofluorescent
Total Gastrin and Acid Outputfrom Acid Secretion with Betazole
TABLE IV
--
1
2
1
mEq H+ ng* gastrin
.02 .Ol
.02 .Ol
2. .7
mEq H+ ng gastrin
.05 .Ol
.04 .Ol
0
mEq H+ ng gastrin
0 .Ol
0 0
mEq H+ ng gastrin
.04 .Ol
0 .Ol
2 3
4
“Geometric Probability
.____* Nanogram.
338
of
Betarole Stimulation --__
-_-__
1
_--.-_--
Pouch after Stimulation
Fifteen Minute Collection Periods ----.
---
Control ____. Dog -.--_-.-----
Heidenhain
gastrin cells. In the antrum there were many such cells and a large amount of gastrin, whereas the fundic mucosa contained a very small amount of gastrin and only a very rare identifiable gastrin cell. Thus the significant quantities of gastrin in the gastric juice of the dog must have their origin in the antral portion of the stomach. The small total amount of gastrin contained in the secretions from antral pouches precludes the origin of large quantities of gastrin in gastric juice arising from a few residual antral cells in the gastric fistula or Heidenhain pouch. Therefore, even if it was possible for some gastrin to enter the gastric lumen directly from the gastrin cell, the large quantity of gastrin in the gastric juice of a gastric fistula that was completely
--.--
2 .7
235
.2
.4 .3
.? 1.4
.6 2.3
.8
1.0 203
179 .7 4.8
1.0 2.1
6
.6 146
1.0 4.0
.8 86
5
.? 116
.9 3.2
.7 45
4
.9 11
.7 .3
.Ol 4
3
.8 1.1
1
.4 87
.5
.5 .l
.493
.5 .2
.5 .6
.819
75 .4 .2 .7
91 .J 10.2
8
Correlation between Acid and Gastrin Output
.8
1.0 137
.774
.a 3.0
.9 3.0
.436
283
means”
.663 <.05
---~-.___
The
American Journal
01 Surgery
Origin of Gastrin
separated from the antrum by a mucosal diaphragm and in the gastric juice of a Heidenhain pouch that was completely separated from the rest of the stomach precluded the possibility that gastrin gained access to the gastric juice by moving from the gastrin cell directly into the gastric lumen. The results are in keeping with the hypothesis presented earlier that gastrin released into the blood by the antrum is substantially cleared by the fundic mucosa [3]. The positive correlation between the amounts of acid and gastrin in the gastric juice suggests that the elimination of gastrin by the fundus is related to the secretory activity of parietal cells. A decrease in gastrin transport by the fundic mucosa caused by a decrease in gastric secretion might provide an explanation of the finding of Becker, Reeder, and Thompson [12] that the gastrin content of the fundic mucosa increased after vagotomy. Summary
Four dogs were prepared with an isolated, innervated antral pouch, a Heidenhain pouch, and a gastric fistula. Gastric secretion was stimulated by perfusion of the antrum with a suspension of liver powder or by betazole injection. Both methods of gastric stimulation increased acid and gastrin output from the gastric fistulas and Heidenhain pouches. There was a significant direct correlation between these two variables in the gastric juice of the gastric fistulas and Heidenhain pouches. We conclude from this study that gastrin in the gastric
Volume 129, September 1974
juice originates in the antrum or some extragastric source and is cleared from the blood by the fundic mucosa. Its rate of appearance in t.he gastric juice is directly related to the secretory activity of the parietal cells. References 1. Jordan PH Jr, Yip BSSC: The presence of gastrin in fasting and stimulated gastric juice of man. Surgery 72: 352, 1972. 2. Jordan PH Jr, Yip BSSC: The canine secretory response to gastrin extracted from gastric juice of man. Surgery 72: 624, 1972. 3. Yip BSSC, Jordan PH Jr: The recovery of intravenously administered radiolabeled gastrin in gastric juice of dogs. Surgery741 412, 1973. 4. Yip BSSC, Jordan PH Jr: Radio-immunoassay of gastrin using antiserum to porcine gastrin. Pfoc Sot fxp Biol Med 134: 380, 1970. 5. Morrison DF: Multivariate Statistical Methods. New York, McGraw-Hill, 1967, p 101. 6. Code CF, Hallenbeck GA, Gregory RA: Histamine content of canine gastric juice. Am J Physiol15 1: 593, 1947. 7. Komorov SA: The action of nitrogenous bases of gastric juice on blood pressure, pancreatic secretion and flow of bile. Am J Physioll15: 604, 1936. 8. Macintosh FC: Histamine as a normal stimulant of gastric secretion. Q J Exp Physiol28: 87, 1938. 9. Ragins H, Dittbrenner M, Lebay P, State D: Observations on the pathway of exogenous Ci4 histamine in stimulating gastric secretion. J Surg Res 4: 164, 1964. 10. Sircus W: Evidence for a gastric secretagogue in the circulation and gastric juice of patients with Zollinger-Ellison syndrome. Lancet 2: 67 1, 1964. 11. McGuigan JE: Gastric mucosal intracellular localization of gastrin by immunofluorescence. Gasfroenferology 55: 315, 1968. 12. Becker HD, Reeder DD, Thompson JC: Effect of vagotomy on gastrin content of gastric fundus and antrum and pancreas in rats. Sufg Forum 24: 359, 1973.
339
Paul H. Jordan, Jr, MD, Houston, Texas Bianca S. S. C. Yip, MD, Houston, Texas
In an earlier study, the presence of gastrin in the gastric juice of human subjects was reported [I]. Subsequently this material was extracted from the gastric juice of a patient with the Zollinger-Ellison syndrome. When tested in dogs, it was equally as potent as pentagastrin in the stimulation of acid secretion [2]. Later it was demonstrated that exogenous gastrin was cleared from the blood by the fundic mucosa [3]. The present study was designed to determine if endogenous gastrin in gastric juice moved directly into the gastric lumen from the antral gastrin cells or was cleared from the blood by the fundic mucosa. Material and Methods Four dogs weighing approximately 20 kg were prepared with a Heidenhain pouch, an innervated antral pouch separated from the fundus by a mucosal bridge, and a gastric fistula of the vagally innervated portion of the stomach. Gastrointestinal continuity was re-established by gastrojejunostomy. Experiments were begun no earlier than three weeks after operation and the dogs were fasted eighteen hours before each experiment. Individual collections of gastric juice from the gastric fistula and the Heidenhain pouch were made continuously every fifteen minutes throughout each experiment. Secretions from antral pouches in response to betazole hydrochloride were small and therefore were collected as one sample for the duration of an experiment.
From the Surgical Services of the Cora and Webb Mading Department of Surgery, Baylor College of Medicine, and the Veterans Administration Hospital, Houston, Texas. Reprint requests should be addressed to Dr Paul Ii. Jordan, Jr, 1200 Moursund Avenue, Houston, Texas 77025.
336
Before initiating an experiment, fifteen minute basal collections were made. The study was not performed until basal secretion from the gastric fistula was less than 0.05 mEq per fifteen minutes. After basal conditions were obtained, gastric secretion was stimulated either by subcutaneous injection of betazole hydrochloride (Histalog) or by constant perfusion of the antrum with a suspension of liver powder. Each stimulant was used in three experiments in each dog. The volume of each fifteen minute collection of gastric juice was measured and an aliquot was titrated with 0.1 N sodium hydroxide to pH 7.0 using an automatic titrator and pH meter (Radiometer, Copenhagen, Denmark). A sample of peripheral venous blood and an aliquot of each collection of gastric juice were analyzed for gastrin by radioimmunoassay [4]. .Results Liver Perfusion. Perfusion of the antrum with a suspension of liver powder produced an increase in gastric secretion from both the gastric fistulas (Table I) and the Heidenhain pouches (Table II). As the acid secretion increased, the concentration and total amount of gastrin in the gastric juice also increased. Because of the wide variation in the amount of gastric juice produced by the different dogs, comparisons between the amounts of acid and gastrin in the gastric juice were determined for each individual dog by the statistical method of Morrison [5]. Analysis indicated that there was a direct correlation between the amounts of acid and gastrin in the gastric juice from both the gastric fistulas and the Heidenhain pouches, which was statistically significant with p values of CO.01 and <0.05, respectively. Serum gastrin levels increased
The American Journal of Surgery
Origin
TABLE
I
Total Gastrin and Acid Output from Gastric Fistula after Stimulation Perfusion
of Gastrin
of Acid Secretion by
of the Antrum with Liver Suspension Fifteen Minute Collection Periods Control 1
2
1
mEq H+ ng* gastrin
.08 .04
.03 .Ol
.2 .4
2
mEq H+ ng gastrin
.13 .04
.02 .Ol
1.0 .6
3
mEq H+ ng gastrin
.05 .03
.Ol .Ol
.4 .l
4
mEq H+ ng gastrin
.Ol .Ol
.02 .Ol
1
“Geometric Probability
Correlation between Acid and Gastrin output
Liver Perfusion
1.1 2%
2
3
4
2.4 397
4.1 1,374
4.0 1,515
4.2 1,599
3.7 1,936
.957
2,911
1.7 2
1.6 338
2.0 257
2.3 506
1.8 574
2.9 1,411
3.1 930
.806
1.0 21
1.7 276
1.9 106
2.8 204
4.0 621
3.9 527
3.6 541
.937
1.9
1.5 22
1.6 31
1.7 37
2.0 69
1.8 109
.561
.7 14
2.0
38
5
5
6
7
8.
5.9
means”
.872 <.Ol
* Nanogram.
Comments
and reached their peak one hour after perfusion of the antrum was begun. Betazole Stimulation. The results obtained by betazole stimulation were similar to those obtained by perfusion of the antrum with liver. There was a direct correlation between the amounts of acid and gastrin in the gastric juice from the gastric fistulas (Table III) and the Heidenhain pouches (Table IV). The correlation between these two variables from both pouches was statistically significant with a p value of
TABLE II
These studies confirm earlier reports [1-31 that gastrin is present in gastric juice. Numerous investigators reported the presence of histamine in gastric juice on bioassay [6-B], but it was subsequently shown that the amount of histamine in gastric juice is insufficient to be detected by bioassay [9J. The presence of gastrin may provide the explanation for the “histamine equivalent” previously reported in canine gastric juice. The possibility of the presence of gastrin in gastric juice was suggested by Sircus [IO] who found a gastric secretagogue in the gastric juice of two patients with the Zollinger-Ellison syndrome. Since gastrin is the secretagogue found in these tumors, it is reasonable to conclude that gastrin in the gastric juice of these Pouch after Stimulation
of Acid Secretion
by
Fifteen Minute CollectionPeriods
1
2
mEq H+ ng* gastrin
.02 .Ol
-01 .Ol
0 0
.08 .03
.25 30.1
.27 35.5
mEq H+ ng gastrin
0 .Ol
0 .Ol
0 0
.58 .OJ
.82 3.1
.81 24.7
mEq H+ ng gastrin
0
0
0
.Ol
0
0
.05 .02
.04 .05
mEq H+ ng gastrin
.03 .Ol
.03 .Ol
.05 .Ol
.16 .25
.17 .92
Dog 1 2 3 4
“Geometric Probability
means” --__
_
Liver Perfusion
Control 1
2
3
4
5
6
7
.32 11.2
.42 67.0
-67 3.9
.58 122
.73 141
.04 .08
.OJ .05
.04 .07
.18 1.25
.22 1.49
.27 1.83
.39
57.2
8 .40 8.0
Correlation between Acid and Gastrin Output
.746
.80
.346
.13 .17
.08 .31
.713
.35 2.64
.38 6.08
24
.868 .709 <.05
* Nanogram.
Volume 128, September 1974
337
Jordan
and Yip
TotalGastrin
TABLE III
and Acid Output from Gastric Fistula after Stimulation
Acid Secretion
of
with Betazole Fifteen Minute Collection Periods
Dog 1
--.~ mEqH+ ng* gastrin
Correlation between Acid and Gastrin output
Betazole Stimulation
Control .___ 1 2
1 _-__
2
3
4
5
6 -
7
8
.08 .04
.lo .04
1.4 2.0
2.9 733
3.8 1,976
3.5 2,345
2.6 7,967
2.4 1,680
2.7 2,260
2.3 1,702
.443
2
mEq H+ ng gastrin
.ll .02
.04 .Ol
.l .l
.8 44
1.2 247
1.6 489
1.7 374
1.1 127
2.0 208
1.4 a4
.770
3
mEq H+ ng gastrin
.07 .03
.04 .Ol
.5 2.0
1.4 38
2.1 153
1.8 627
2.1 647
2.2 990
2.6 749
2.3 698
.860
4
mEq H+ ng gastrin
.06 .05
.02 .Ol
.l 4.0
.6 59
1.4 349
1.5 187
1.2 108
.9 72
1.0 113
1.9 110
.707
“Geometric
means”
.703 <.05
Probability * Nanogram.
patients initiated the gastric secretory response in rats that constituted a positive bioassay for diagnosis of the Zollinger-Ellison syndrome. The increase in gastrin in the gastric juice after betazole stimulation as well as by chemical stimulation of the antral mucosa suggests, as was previously postulated [I], that betazole is a releaser of gastrin from the antrum. The failure to obtain as great a rise in serum gastrin after antral perfusion with liver or after bet,azole injection in dogs compared with that in human subjects suggests that the fundic mucosa may clear the blood of gastrin more efficiently in the dog than it does in man. McGuigan (II] demonstrated a positive correlation between the gastrin content of the gastric wall and the number of specific immunofluorescent
Total Gastrin and Acid Outputfrom Acid Secretion with Betazole
TABLE IV
--
1
2
1
mEq H+ ng* gastrin
.02 .Ol
.02 .Ol
2. .7
mEq H+ ng gastrin
.05 .Ol
.04 .Ol
0
mEq H+ ng gastrin
0 .Ol
0 0
mEq H+ ng gastrin
.04 .Ol
0 .Ol
2 3
4
“Geometric Probability
.____* Nanogram.
338
of
Betarole Stimulation --__
-_-__
1
_--.-_--
Pouch after Stimulation
Fifteen Minute Collection Periods ----.
---
Control ____. Dog -.--_-.-----
Heidenhain
gastrin cells. In the antrum there were many such cells and a large amount of gastrin, whereas the fundic mucosa contained a very small amount of gastrin and only a very rare identifiable gastrin cell. Thus the significant quantities of gastrin in the gastric juice of the dog must have their origin in the antral portion of the stomach. The small total amount of gastrin contained in the secretions from antral pouches precludes the origin of large quantities of gastrin in gastric juice arising from a few residual antral cells in the gastric fistula or Heidenhain pouch. Therefore, even if it was possible for some gastrin to enter the gastric lumen directly from the gastrin cell, the large quantity of gastrin in the gastric juice of a gastric fistula that was completely
--.--
2 .7
235
.2
.4 .3
.? 1.4
.6 2.3
.8
1.0 203
179 .7 4.8
1.0 2.1
6
.6 146
1.0 4.0
.8 86
5
.? 116
.9 3.2
.7 45
4
.9 11
.7 .3
.Ol 4
3
.8 1.1
1
.4 87
.5
.5 .l
.493
.5 .2
.5 .6
.819
75 .4 .2 .7
91 .J 10.2
8
Correlation between Acid and Gastrin Output
.8
1.0 137
.774
.a 3.0
.9 3.0
.436
283
means”
.663 <.05
---~-.___
The
American Journal
01 Surgery
Origin of Gastrin
separated from the antrum by a mucosal diaphragm and in the gastric juice of a Heidenhain pouch that was completely separated from the rest of the stomach precluded the possibility that gastrin gained access to the gastric juice by moving from the gastrin cell directly into the gastric lumen. The results are in keeping with the hypothesis presented earlier that gastrin released into the blood by the antrum is substantially cleared by the fundic mucosa [3]. The positive correlation between the amounts of acid and gastrin in the gastric juice suggests that the elimination of gastrin by the fundus is related to the secretory activity of parietal cells. A decrease in gastrin transport by the fundic mucosa caused by a decrease in gastric secretion might provide an explanation of the finding of Becker, Reeder, and Thompson [12] that the gastrin content of the fundic mucosa increased after vagotomy. Summary
Four dogs were prepared with an isolated, innervated antral pouch, a Heidenhain pouch, and a gastric fistula. Gastric secretion was stimulated by perfusion of the antrum with a suspension of liver powder or by betazole injection. Both methods of gastric stimulation increased acid and gastrin output from the gastric fistulas and Heidenhain pouches. There was a significant direct correlation between these two variables in the gastric juice of the gastric fistulas and Heidenhain pouches. We conclude from this study that gastrin in the gastric
Volume 129, September 1974
juice originates in the antrum or some extragastric source and is cleared from the blood by the fundic mucosa. Its rate of appearance in t.he gastric juice is directly related to the secretory activity of the parietal cells. References 1. Jordan PH Jr, Yip BSSC: The presence of gastrin in fasting and stimulated gastric juice of man. Surgery 72: 352, 1972. 2. Jordan PH Jr, Yip BSSC: The canine secretory response to gastrin extracted from gastric juice of man. Surgery 72: 624, 1972. 3. Yip BSSC, Jordan PH Jr: The recovery of intravenously administered radiolabeled gastrin in gastric juice of dogs. Surgery741 412, 1973. 4. Yip BSSC, Jordan PH Jr: Radio-immunoassay of gastrin using antiserum to porcine gastrin. Pfoc Sot fxp Biol Med 134: 380, 1970. 5. Morrison DF: Multivariate Statistical Methods. New York, McGraw-Hill, 1967, p 101. 6. Code CF, Hallenbeck GA, Gregory RA: Histamine content of canine gastric juice. Am J Physiol15 1: 593, 1947. 7. Komorov SA: The action of nitrogenous bases of gastric juice on blood pressure, pancreatic secretion and flow of bile. Am J Physioll15: 604, 1936. 8. Macintosh FC: Histamine as a normal stimulant of gastric secretion. Q J Exp Physiol28: 87, 1938. 9. Ragins H, Dittbrenner M, Lebay P, State D: Observations on the pathway of exogenous Ci4 histamine in stimulating gastric secretion. J Surg Res 4: 164, 1964. 10. Sircus W: Evidence for a gastric secretagogue in the circulation and gastric juice of patients with Zollinger-Ellison syndrome. Lancet 2: 67 1, 1964. 11. McGuigan JE: Gastric mucosal intracellular localization of gastrin by immunofluorescence. Gasfroenferology 55: 315, 1968. 12. Becker HD, Reeder DD, Thompson JC: Effect of vagotomy on gastrin content of gastric fundus and antrum and pancreas in rats. Sufg Forum 24: 359, 1973.
339