Atta physiol. stand. 1977. 99. 510-512 From the Department of Pharmacology, Karolinska lnstitutet, Stockholm, Sweden
Increase in Gastrin Concentration in the Duodenal Mucosa of Dogs Following Resection of the Gastric Antrum By
GORANNILSSON and KERSTIN BRODIN
The results of studies using biological (for a review see E m i s and Fyro 1968) o r radioinimunological (Nilsson, Yalow and Berson 1973, Thompson et al. 1973) assay methods indicate that there is gastrin in the duodenal mucosa of dogs. In the dog, the amount of gastrin contained in the duodenum is very much smaller than that found in the antral mucosa (Nilsson ct al. 1973). However, several studies indicate that gastrin of duodenal origin niay be released and be of importance for the activation of the HCI glands. Thus, there is a significant residual acid response to sham feeding in dogs following resection of the gastric antrum (Olbe 1964, Sjodin 1972). This response is almost abolished o n subsequent removal of the duodenal bulb (Olbe 1964). Recently, i t was demonstrated in dogs that basal plasma levels of gastrin are not decreased following antral resection. The results also showed that test meal stimulation in antrectomized dogs evokes a significant elevation of the plasma gastrin level. Subsequent removal of the duodenal bulb lowered the basal gastrin levels and no elevation was seen in dogs that were given a test meal. The above results suggest that duodenal gastrin, and in particular gastrin from the duodenal bulb, is released on physiological stimulation. The amounts of gastrin released were surprisingly large, considering the small amounts of gastrin normally found in the duodenal mucosa in dogs (Sjodin and Nilsson 1975). The possibility exists that following resection of the antrum the duodenal rnucosa increases its production of gastrin. The present study was undertaken to compare the amounts of gastrin that are present in the duodenal mucosa in normal dogs and in dogs that have undergone surgical resection of the gastric antrum. Thwi
1. Amounts of gastrin (nanogram) in duodenal mucosa of dogs.
Control dogs
Proximal duodenum Middle duodenum Distal duodenum
510
Antrum resected dogs
A
B
C
D
E
F
55 28 2
37 8
42 24 1
5 000 50 28
370 6
1
2000 14 6
2
51 1
DUODENAL GASTRIN 2 500
2000
v)
U I
g
1500
0
U
z
f
1000
b-
"U I
Fig. 1. Amounts (nanograms) of gastrin extracted from the proximal (P), middle (M) and distal ( D ) portions of the duodenum from normal dogs (A-C) and dogs (D-F) that have undergone antrum resection prior to extraction of the duodenum.
500
P
Y
In 3 dogs the gastric antrum was resected and the gastrointestinal continuity restored by gastroduodenostomy. Following recovery for 7-8 weeks, the dogs were anaesthetized by i.v. injection of Nembutal (30 mglkg). T h e duodenum was removed, divided into lhree portions, frozen o n dry ice and stored a t - 20°C prior to extraction with boiling water for 10 min. The extracts were filtered through gauze, frozen a n d stored at -2O'C until assayed for gastrin content by radioimmunoassay (Nilsson 1975). Another 3 dogs that had not undergone gastric surgery were treated in the same way.
The present results are consistent with our previous findings using a radioimmunological technique (Nilsson et al. 1973) that there exists a gastrin concentration gradient within the dog duodenum, the highest concentrations being found in the proximal portion of the duodenum. The amounts of gastrin extracted from the upper duodenum from antrectomized dogs were on the average 55 times larger than those extractcd from the same part of the duodenum of unoperated dogs. The amounts of gastrin found in extracts from lower portions of the duodenum were, however, similar in both groups of dogs (Table 1, Fig. I). The finding that gastrin concentrations in the proximal portion of the duodenum are greatly increased in dogs that have undergone resection of the antrum offers a n explanation to our previous observation that basal plasma gastrin concentrations remain at preoperative levels in antrectomized dogs and are reduced following subsequent resection of the duodenal bulb (Sjodin and Nilsson 1975). The present results also provide an explanation of our finding that there is a considerable elevation of the plasma gastrin level in antrectomi7ed dogs following stimulation with a test meal and explain why this response is eliminated following removal of the duodenal bulb. Together with our previous study (Sjodin and Nilsson 1975), the results suggest that there are mechanisms that, when activated, may increase the concentration of gastrin in the proximal portion of the duodenum of the dog. This study was supported by grants from the Swedish Medical Research Council (Proj. no. 04X-3521) The technical and secretarial assistance of Miss Gunilla Thulin, Miss Elisabet Tircn, Mrs Inga-Lill Glans and Mrs Birgitta Pilarp is gratefully acknowledged.
512
GORAN NILSSON AND KERSTIN BRODIN
References EuAs, S . and 9.FuRB, Gastrin-like activity in different parts of the gastrointestinal tract of the cat. Acra plfl,sio/.sconcl. 1968. 71. 359-367. G., Increased plasma gastrin levels in connection with inhibition of gastric acid responses to NILSSOV, sham feeding follofiing bulbar perfusion with acid i n dogs. Scnnd. J . Ga.trroent. 1975. 10. 273-278. NILSSON, G.. R. S. YALOW and S. A. BERSON,Distribution of gastrin in the gastrointestinal tract of human, dog. cat and hog. NohPl.\~,ntpnsiut?tX V I . Almqvist & Wiksell, Stockholm, 1973. 223-238. OLEE,L., Effect of resection of gastrin releasing regions on acid response to sham feeding and insulin hypoglycemia in Pavlov pouch dogs. Actn physiol. scand. 1964. 62. 169-175. SJ~DIX L.,. Potentiation of the gastric secretory response to sham feeding in dogs by infusions of gastrin and pentagastrin. A i , t ~plfrsiol. scanrl. 1972. 85. 24-32. SJODI?I.L. and G . NILSSON. Role of antrum and duodenum in the control of postprandial gastric acid secretion and plasma gastrin concentration in dogs. GastroentcwJ~ogy1975. 69. 928-934. T m M P 9 0 N , J . C., D . D . RELIXK, W. D. DAVIDSON, B. M. JACKSOX and B. G. CLENDINNEU, Studies o n the metabolism of gastrin. I~~hels!.nfposiirr,r X V I . Almqvist & Wiksell, Stockholm 1973. 1 1 1-135.
Increase in Gastrin Concentration in the Duodenal Mucosa of Dogs Following Resection of the Gastric Antrum By
GORANNILSSON and KERSTIN BRODIN
The results of studies using biological (for a review see E m i s and Fyro 1968) o r radioinimunological (Nilsson, Yalow and Berson 1973, Thompson et al. 1973) assay methods indicate that there is gastrin in the duodenal mucosa of dogs. In the dog, the amount of gastrin contained in the duodenum is very much smaller than that found in the antral mucosa (Nilsson ct al. 1973). However, several studies indicate that gastrin of duodenal origin niay be released and be of importance for the activation of the HCI glands. Thus, there is a significant residual acid response to sham feeding in dogs following resection of the gastric antrum (Olbe 1964, Sjodin 1972). This response is almost abolished o n subsequent removal of the duodenal bulb (Olbe 1964). Recently, i t was demonstrated in dogs that basal plasma levels of gastrin are not decreased following antral resection. The results also showed that test meal stimulation in antrectomized dogs evokes a significant elevation of the plasma gastrin level. Subsequent removal of the duodenal bulb lowered the basal gastrin levels and no elevation was seen in dogs that were given a test meal. The above results suggest that duodenal gastrin, and in particular gastrin from the duodenal bulb, is released on physiological stimulation. The amounts of gastrin released were surprisingly large, considering the small amounts of gastrin normally found in the duodenal mucosa in dogs (Sjodin and Nilsson 1975). The possibility exists that following resection of the antrum the duodenal rnucosa increases its production of gastrin. The present study was undertaken to compare the amounts of gastrin that are present in the duodenal mucosa in normal dogs and in dogs that have undergone surgical resection of the gastric antrum. Thwi
1. Amounts of gastrin (nanogram) in duodenal mucosa of dogs.
Control dogs
Proximal duodenum Middle duodenum Distal duodenum
510
Antrum resected dogs
A
B
C
D
E
F
55 28 2
37 8
42 24 1
5 000 50 28
370 6
1
2000 14 6
2
51 1
DUODENAL GASTRIN 2 500
2000
v)
U I
g
1500
0
U
z
f
1000
b-
"U I
Fig. 1. Amounts (nanograms) of gastrin extracted from the proximal (P), middle (M) and distal ( D ) portions of the duodenum from normal dogs (A-C) and dogs (D-F) that have undergone antrum resection prior to extraction of the duodenum.
500
P
Y
In 3 dogs the gastric antrum was resected and the gastrointestinal continuity restored by gastroduodenostomy. Following recovery for 7-8 weeks, the dogs were anaesthetized by i.v. injection of Nembutal (30 mglkg). T h e duodenum was removed, divided into lhree portions, frozen o n dry ice and stored a t - 20°C prior to extraction with boiling water for 10 min. The extracts were filtered through gauze, frozen a n d stored at -2O'C until assayed for gastrin content by radioimmunoassay (Nilsson 1975). Another 3 dogs that had not undergone gastric surgery were treated in the same way.
The present results are consistent with our previous findings using a radioimmunological technique (Nilsson et al. 1973) that there exists a gastrin concentration gradient within the dog duodenum, the highest concentrations being found in the proximal portion of the duodenum. The amounts of gastrin extracted from the upper duodenum from antrectomized dogs were on the average 55 times larger than those extractcd from the same part of the duodenum of unoperated dogs. The amounts of gastrin found in extracts from lower portions of the duodenum were, however, similar in both groups of dogs (Table 1, Fig. I). The finding that gastrin concentrations in the proximal portion of the duodenum are greatly increased in dogs that have undergone resection of the antrum offers a n explanation to our previous observation that basal plasma gastrin concentrations remain at preoperative levels in antrectomized dogs and are reduced following subsequent resection of the duodenal bulb (Sjodin and Nilsson 1975). The present results also provide an explanation of our finding that there is a considerable elevation of the plasma gastrin level in antrectomi7ed dogs following stimulation with a test meal and explain why this response is eliminated following removal of the duodenal bulb. Together with our previous study (Sjodin and Nilsson 1975), the results suggest that there are mechanisms that, when activated, may increase the concentration of gastrin in the proximal portion of the duodenum of the dog. This study was supported by grants from the Swedish Medical Research Council (Proj. no. 04X-3521) The technical and secretarial assistance of Miss Gunilla Thulin, Miss Elisabet Tircn, Mrs Inga-Lill Glans and Mrs Birgitta Pilarp is gratefully acknowledged.
512
GORAN NILSSON AND KERSTIN BRODIN
References EuAs, S . and 9.FuRB, Gastrin-like activity in different parts of the gastrointestinal tract of the cat. Acra plfl,sio/.sconcl. 1968. 71. 359-367. G., Increased plasma gastrin levels in connection with inhibition of gastric acid responses to NILSSOV, sham feeding follofiing bulbar perfusion with acid i n dogs. Scnnd. J . Ga.trroent. 1975. 10. 273-278. NILSSON, G.. R. S. YALOW and S. A. BERSON,Distribution of gastrin in the gastrointestinal tract of human, dog. cat and hog. NohPl.\~,ntpnsiut?tX V I . Almqvist & Wiksell, Stockholm, 1973. 223-238. OLEE,L., Effect of resection of gastrin releasing regions on acid response to sham feeding and insulin hypoglycemia in Pavlov pouch dogs. Actn physiol. scand. 1964. 62. 169-175. SJ~DIX L.,. Potentiation of the gastric secretory response to sham feeding in dogs by infusions of gastrin and pentagastrin. A i , t ~plfrsiol. scanrl. 1972. 85. 24-32. SJODI?I.L. and G . NILSSON. Role of antrum and duodenum in the control of postprandial gastric acid secretion and plasma gastrin concentration in dogs. GastroentcwJ~ogy1975. 69. 928-934. T m M P 9 0 N , J . C., D . D . RELIXK, W. D. DAVIDSON, B. M. JACKSOX and B. G. CLENDINNEU, Studies o n the metabolism of gastrin. I~~hels!.nfposiirr,r X V I . Almqvist & Wiksell, Stockholm 1973. 1 1 1-135.
