Antrectomized Rats Research Articles

Mobilization of gastric histamine during repeated administration of a proton potassium adenosine triphosphatase inhibitor in intact and antrectomized rats

Intact and antrectomized female rats were treated with the potent proton pump inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin concentration and urinary excretion of N-terminal big gastrin increased until day 14 and persisted at a high level in intact rats treated with E3810, but did not increase in antrectomized rats. Urinary excretion of histamine increased progressively and reached 7 times the control value following 4 weeks of treatment with E3810 in intact rats, but not in antrectomized rats. At the termination of the treatment, the endocrine cell density in the oxyntic mucosa of intact rats had increased by 85% with increased histamine content and elevated histidine decarboxylase activity, while antrectomized rats showed a low histamine level and low histidine decarboxylase activity. Administration of gastrin-17 I (10 μg/kg weight, sc) itself caused a significant increase in urinary excretion of histamine, which was inhibited by the specific gastrin receptor antagonist, L-365,260. These results suggests that the massive urinary excretion of histamine caused by the treatment with E3810 reflects gastrin-induced mobilization of gastric histamine and that neither E3810 itself nor E3810-induced luminal pH elevation has direct effects on mobilization of oxyntic mucosal histamine.

Effect of antrectomy and drug-induced achlorhydria on urinary excretion of N-terminal big gastrin immunoreactivity in rats

Immunoreactivities of urinary N-terminal big gastrin and serum C-terminal gastrin were determined in intact and antrectomized rats by radioimmunoassay using two antisera specific for N- and C-termini of big gastrin, respectively. Gel filtration of urine extract from intact rat showed a single giant peak of N-terminal big gastrin immunoreactivity eluted in a later position than 1–17 gastrin-34, indicating that N-terminal peptides smaller than 1–17 gastrin-34 are excreted in urine. Serum C-terminal gastrin concentration in antrectomized rats was about one sixth that in intact rats. Urinary excretion of N-terminal big gastrin in antrectomized rats was about one sixth that in intact rats. 2 week treatment with E3810, a proton pump inhibitor, (40 mg/kg/day, s.c.) induced urinary excretion of N-terminal big gastrin in parallel with a marked increase in serum C-terminal gastrin concentration in intact rats. Antrectomy completely prevented both the increase in urinary excretion of N-terminal big gastrin and the elevation of serum C-terminal gastrin induced by administration of E3810. There was an excellent correlation between serum concentration of C-terminal gastrin and urinary excretion of N-terminal big gastrin. These results suggest that urinary N-terminal big gastrin, which mostly originates from the gastric antrum, is a useful indicator of gastrin secretion in the rat.

Gastrin stimulates the self-replication rate of enterochromaffinlike cells in the rat stomach: Effects of omeprazole, ranitidine, and gastrin-17 in intact and antrectomized rats

The enterochromaffinlike cells in the rat stomach are rich in histamine and are thought to be under the influence of gastrin. The effect of sustained endogenous and exogenous hypergastrinemia on the activity and proliferation rate of the enterochromaffinlike cells was studied by determining the histidine decarboxylase activity and histamine concentration and by combining histamine immunocytochemistry and autoradiography after in vivo labeling with [3H]thymidine. The proliferation rate of the stem cells in the oxyntic mucosal progenitor zone was also studied. Exogenous hypergastrinemia was induced by infusion of rat gastrin-17 (60 nmol · kg−1 · day−1). Endogenous hypergastrinemia was induced by inhibition of gastric acid secretion with omeprazole (80 μmol · kg−1 · day−1) or ranitidine (1200 μmol · kg−1 · day−1). The effect of omeprazole was also studied in antrectomized rats. In intact rats, all treatments resulted in elevated plasma gastrin levels and were accompanied by an increase in the histidine decarboxylase activity and the histamine content of the oxyntic mucosa. This resulted in an increase in the enterochromaffinlike cell proliferation rate, leading to enterochromaffinlike cell hyperplasia. The number of labeled stem cells was increased, but this effect was not as pronounced as in the enterochromaffinlike cells. In antrectomized rats, the inhibition of acid secretion by omeprazole did not result in elevated plasma gastrin or in an increase in the activity or number of enterochromaffinlike cells, indicating that omeprazole per se had no effect on these cells. These data support the view that gastrin stimulates the proliferation rate of both enterochromaffin-like cells and stem cells. Gastrin also stimulates the activity of the enterochromaffinlike cells.

Cholecystokinins but not gastrin-17 release calcitonin from thyroid C-cells in the rat

Subcutaneous injections of gastrin-17, cholecystokinin-39, cholecystokinin-8 (sulfated and non-sulfated forms), cholecystokinin-4 or pentagastrin induced hypocalcemia in rats. The hypocalcemia was associated with calcitonin release for pentagastrin and the cholecystokinins but not for gastrin-17, even at very high doses. Permanent hypergastrinemia, induced by surgical removal of the acid-producing part of the stomach (fundectomy) or by treatment with high doses of omeprazole, a blocker of acid secretion, was not accompanied by elevated plasma calcitonin. Long-lasting hypergastrinemia is known to cause hyperplasia of gastrin-sensitive endocrine cells in the rat stomach while hypogastrinemia does the reverse. In antrectomized rats, having low serum gastrin, and in fundectomized rats, having high serum gastrin, the serum calcitonin concentration, the thyroid calcitonin content and the number of C-cells remained as in sham-operated controls two months after the operations. We conclude that neither exogenous nor endogenous gastrin stimulates calcitonin secretion in the rat and that long-standing hypo- or hypergastrinemia is without effect on the number of thyroid C-cells. Our results, however, do not exclude the possibility that the cholecystokinins might act as calcitonin secretagogues in the rat although such a role remains to be established.

Role of the proximal duodenum in gastrin regulation following antrectomy.

Antrectomy is accepted as the most effective surgical treatment of recurrent duodenal ulcer after complete vagotomy. Although antrectomy is aimed at reducing serum gastrin levels, both human and experimental reports seem to indicate that gastrin concentrations may be unchanged following this operation. The probable source of gastrin has been considered to be the proximal third of the duodenum, since at this level increased tissue gastrin concentrations were found after antrectomy. The present study was carried out in order to gain insight into the mechanism by which the duodenum may compensate for the removal of the antrum. Forty white rats were randomly divided into two equal groups and underwent antrectomy with gastroduodenostomy or simple laparotomy. Three to four months after surgery, serum gastrin determinations were carried out by radioimmunoassay both in fasted and freely fed rats. The duodenum was then removed and its proximal third was used for G cell counts (immunoperoxidase method) and for assessment of G cell cytoplasmic granule distribution (electron-microscopic examination). Antrectomy significantly increased fasting serum gastrin levels (p less than 0.01), while it completely abolished the gastrin response to food ingestion (p less than 0.001). In antrectomized rats, the duodenal G cell number was significantly higher than in control rats (p less than 0.001), whilst the G cell cytoplasmic granule number remained unchanged. In conclusion, the present study indicates that in the rat the proximal duodenum increases its content of tissue gastrin following antrectomy mainly by enhancing the regional G cell density.

Insulin-induced gastric ulcers in the rat.

Low doses of insulin (less than 1.25 IU/kg body weight) stimulate gastric acid secretion in the rat, whereas higher doses (greater than 2.5 IU/kg) release gastrin and cause gastric ulcers but do not increase acid secretion. In this study we have characterized the ulcerogenic properties of insulin in the rat. A dose of 5 IU/kg subcutaneously proved to be maximally effective. Ulcer formation was rapid, and the maximum 90% incidence was reached after 5 h. Both glucose administration and food intake protected against the ulcerogenic effects of insulin. The effects of anti-ulcer drugs and of vagotomy on insulin-induced ulcers were also studied. Animals were divided into seven groups: 1) saline, 2) omeprazole, 3) ranitidine, 4) sucralfate, 5) bilateral vagotomy, 6) unilateral vagotomy, and 7) antrectomy. Medical treatment was continued for 6 days before insulin administration, operations having been performed 6-8 weeks earlier. Insulin was injected subcutaneously in a dose of 5 IU/kg. Five hours later stomachs were inspected for ulcers. Neither the antrectomized rats nor those treated with omeprazole or ranitidine had ulcers. In the saline- and the sucralfate-treated groups the gastric ulcer incidence was 83% and 80%, respectively, with a mean of six and seven ulcers per rat. Ulcers were evenly distributed between the two sides of the stomach. Rats that had undergone bilateral vagotomy (which abolishes gastric acid secretion and causes hypergastrinemia) responded to insulin with an ulcer incidence of 5%. In the unilaterally vagotomized rats there were only 2 ulcers on the denervated compared with 37 on the innervated side.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation: Studies with omeprazole and ranitidine in intact and antrectomized rats

Unoperated female rats were subjected to daily oral treatment with omeprazole (10 or 400 μmol/kg body wt), ranitidine (175 + 175 + 350 μmol/kg body wt), or vehicle and antrectomized rats were treated with omeprazole (400 μmol/kg body wt) or vehicle. After 10 wk of treatment, plasma gastrin levels were high in unoperated rats treated with the high omeprazole dose and with ranitidine, and low in antrectomized controls. Plasma gastrin levels were slightly higher in the low-dose omeprazole group than in the intact controls. In antrectomized rats treated with the high dose of omeprazole, the plasma gastrin level was in the same range as in intact control rats. A close correlation (r = 0.89, p < 0.0001) was found between the plasma gastrin level and the oxyntic mucosal enterochromaffinlike cell density (as well as the tissue levels of histidine decarboxylase and histamine in the oxyntic mucosa) in all groups. The somatostatin cell density in the oxyntic mucosa was not altered by the various treatments. During a recovery period of 10 wk after the 10-wk treatment, the enterochromaffinlike cell density and histamine concentration decreased by 30%–40% in the rats treated with the high dose of omeprazole, whereas the corresponding values increased by 50% and 40%, respectively, in the control rats. The difference between the two groups, however, was still statistically significant. Plasma gastrin levels and gastric histidine decarboxylase activity returned to control values during recovery. The results suggest that the observed changes in enterochromaffinlike cell density are related to the plasma gastrin levels and that they are reversible. It is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of enterochromaffinlike cells.

Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation

Abstract Unoperated female rats were subjected to daily oral treatment with omeprazole (10 or 400 μmol/kg body wt), ranitidine (175 + 175 + 350 μmol/kg body wt), or vehicle and antrectomized rats were treated with omeprazole (400 μmol/kg body wt) or vehicle. After 10 wk of treatment, plasma gastrin levels were high in unoperated rats treated with the high omeprazole dose and with ranitidine, and low in antrectomized controls. Plasma gastrin levels were slightly higher in the low-dose omeprazole group than in the intact controls. In antrectomized rats treated with the high dose of omeprazole, the plasma gastrin level was in the same range as in intact control rats. A close correlation (r = 0.89, p

Stimulation of mucosal growth by a dietary amine.

Nutrients are believed to have a direct trophic effect on the cells of the gastrointestinal mucosa. However, no normal constituent of the diet has ever been shown to stimulate mucosal growth when administered orally. Sham-operated and antrectomized rats were fed 20 g of powdered commercial rat pellets daily or 20 g of food containing dimethylamine (100 mumol/g food). After 7 days rats were killed and growth of the mucosa of the oxyntic gland portion of the stomach and 2-cm segments of duodenum, jejunum, and proximal colon was determined. Antrectomy resulted in significant decreases in the weight and the DNA, RNA, and protein content of all four tissues and serum gastrin levels. Feeding amines abolished the differences in the oxyntic gland and duodenal mucosa. In general, the effect of amines decreased distally. Feeding amines did not significantly alter serum gastrin levels. These data indicate that dietary amines may directly stimulate the growth of gastrointestinal mucosa. These results may explain some of the proximal-to-distal gradients described for the growth of the mucosa.

Role of gastrin in gastrointestinal adaptation after small bowel resection.

Gastrin is a trophic hormone for the mucosa of the oxyntic gland area of the stomach, the proximal small intestine, and the colon. It also has trophic effects on the pancreas. All these tissues undergo hyperplasia to some extent following distal small bowel resection. This study evaluates the role of gastrin in postresectional hyperplasia by examining the growth of these tissues in antrectomized rats following intestinal resection. Antrectomy itself caused atrophy of the oxyntic gland mucosa, colonic mucosa, and the pancreas but had no effect on ileal mucosa. Resection by itself stimulated growth of all tissues and significantly increased serum gastrin levels. After resection in antrectomized animals, all tissues underwent an adaptational response. The increase in total DNA content after resection in antrectomized rats was as great in all tissues, except the colon, as it was in animals with intact antrums and normal gastrin levels. These results indicate that gastrin plays no role in the postresectional hyperplasia observed in the various tissues of the gastrointestinal tract.

Suppression of gastric acid secretory and ulcerogenic effects of cysteamine in chronic antrectomized rat

The secretory and ulcerogenic effects of cysteamine were studied in normal and in chronically antrectomized rats. In agreement with the results obtained by other authors, cysteamine increased gastric acid secretion and induced duodenal ulcers. In our experiments hexamethonium, atropine and vagotomy had no effect on the hypersecretion induced by cysteamine. Acid hypersecretion was reduced in a dose-related manner by cimetidine and proglumide, the last claimed to be an antigastrin drug. Antrectomy completely blocked acid hypersecretion in both anaesthetized and conscious rats given cysteamine and protected conscious animals from cysteamine ulcer formation. It is worth stressing that chronically antrectomized rats were still able to respond to histamine infusion with acid hypersecretion. These results suggest that cysteamine may act mainly on the antrum probably inducing a release of gastrin. To confirm this hypothesis blood gastrin levels in normal and antrectomized rats during cysteamine treatment should be measured.

Effects of insulin on serum gastrin concentrations, gastric acid secretion and histamine mobilization in the rat.

Small doses of insulin (&lt;1.25 U/kg) caused hypoglycemia, stimulated gastric acid secretion slightly, activated gastric mucosal histidine decarboxylase moderately, and enhanced the pentagastrin‐induced activation of histidine decarboxylase. Large doses of insulin (&gt;2.5 U/kg) caused marked hypoglycemia and hypergastrinemia. Moreover, it lowered gastric mucosal histamine concentration and greatly activated histidine decarboxylase. Gastric acid secretion was not stimulated. Pentagastrin‐stimulated acid secretion was blocked and histamine‐stimulated secretion slightly inhibited. Combined administration of insulin and glucose prevented the acid response (insulin dose 0.6 U/kg) and the activation of histidine decarboxylase but not the hypergastrinemia (2.5 U/kg). Paradoxically, combined treatment with insulin and glucose did not prevent pentagastrin from activating histidine decarboxylase. Glucose alone raised the serum gastrin concentration in both unoperated and vagotomized rats. The histidine decarboxylase activity was not raised. Glucose inhibited the pentagastrin‐induced release of histamine greatly but inhibited the pentagastrin‐induced enzyme activation only moderately. In antrectomized rats, large doses of insulin (&gt;1.25 U/kg) had no effect on the serum gastrin concentration but stimulated gastric acid secretion in contrast to what was the case in unoperated rats. Glucose prevented the acid response to insulin. The gastric histidine decarboxylase was not activated by insulin following antrectomy. In vagally denervated rats, insulin (5 U/kg) increased the serum gastrin concentration slightly but did not raise the histidine decarboxylase activity. We interpret the results as follows: With small doses of insulin the gastric secretagogue effect is attributable mainly to vagal nerve stimulation evoked by the hypoglycemia. With large doses of insulin there is no acid response. The effects on the parietal cells of the ensuing hypergastrinemia are counteracted by an unknow mechanism, which however does not prevent gastrin from releasing gastric histamine and stimulating gastric histidine decarboxylase. The insulin‐induced release of gastrin is not elicited exclusively through vagal excitation by hypoglycemia, since insulin releases gastrin also after vagotomy and after glucose administration. The great enzyme‐activating effect of insulin is a consequence of gastrin release. In addition, however, insulin seems to enhance the responsiveness of the enzyme‐containing cells to gastrin. Insulin is a poor substitute for vagal excitation in that it exerts a number of actions which are unrelated to vagal excitation.

The influence of starvation on intestinal cholecystokinin-like activity and pancreatic growth.

1. This study examines the influence of starvation on intestinal CCK content and pancreatic growth. Intestinal CCK content was determined by measuring the CCK-like activity using an in vitro gall-bladder bio-assay. Starvation for up to 72 hr causes a parallel fall in intestinal CCK content and pancreatic DNA synthesis. Since there was no significant decrease in liver DNA synthesis, the effect of starvation was probably not simply a consequence of malnutrition. Furthermore there was little effect of starvation on pancreatic protein and DNA content, suggesting that pancreatic cell turnover is particularly sensitive to changes in dietary stimulation.2. With refeeding after starvation CCK-like activity in intestinal extracts gradually increased, approaching non-fasting levels 72 hr after refeeding. Pancreatic DNA synthesis also returned to non-fasting levels after feeding but this rose faster than the intestinal CCK content.3. Pentagastrin treatment prevented the atrophy of both the pancreas and the gastrointestinal tract with starvation without influencing the fall in intestinal CCK-like activity. This suggests that the control of CCK-containing cells is different from that of the surrounding intestinal parenchyma.4. The effect of starvation was also studied in antrectomized rats. Antrectomy alone did not reduce pancreatic DNA synthesis although DNA synthesis of the small intestine was significantly reduced. When antrectomized rats were starved pancreatic DNA synthesis fell to the same degree as was found in unoperated animals. The pancreatic atrophy was also accompanied by a drop in intestinal CCK content. Starvation of antrectomized rats, however, did not further depress the already greatly reduced plasma gastrin concentration.

Changes in gastrin levels, food intake, and duodenal mucosal growth during lactation.

Gastrointestinal epithelial cell proliferation is stimulated during lactation in the rat. Serum gastrin levels and food intake are also increased during lactation. We investigated the role of gastrin and food intake as possible mediators of duodenal mucosal growth during the first 15 days of lactation. As the lactation period progressed, significant increases in the following crypt properties were noted: 1) crypt length; 2) cells/crypt; 3) labeling index; and 4) dimensions of the proliferative zone. Maternal serum gastrin levels rose abruptly by the first day of birth and remained elevated throughout lactation. The increases in crypt cell proliferation significantly correlated with food intake but not with serum gastrin levels during lactation. Mucosal mass and villus-crypt dimensions were also significantly increased above virgin levels in lactating antrectomized rats. These results suggest that the increase in duodenal growth during lactation most probably is not mediated by postpartum hypergastrinemia and that the increase in cell proliferation may be a direct response to an enhancement in food intake.

Interrelationships between the gastric secretory responses, prostaglandin E2 inhibition and serum level of immunoreactive gastrin in pylorus-ligated and antrectomized rats.

The effects of prostaglandin E2 (PGE2) have been studied on the gastric secretion and the serum level of immunoreactive gastrin in pylorus-ligated and antrectomized rats. It has been observed that: (1) a significant inhibition of gastric secretion (volume and acid output) was caused by PGE2, applied in doses of 75, 150 and 300 microgram/kg body weight, subcutaneously, in both pylorus-occluded and antrectomized rats: PGE2 inhibition of gastric secretion was more pronounced in rats with antrectomy; (2) no significant changes were found in the serum gastrin levels of both pylorus-ligated and antrectomized rats, and (3) no significant changes in serum levels of immunoreactive gastrin were produced by different doses of PGE2, in comparison with their marked inhibitory effects on gastric H+ secretion. It was concluded that there is no essential role of the immunoreactive gastrin, originated from the antral part of the stomach, neither in development of gastric hypersecretion nor in PGE2-produced inhibition on gastric secretion of the pylorus-occluded rats.

Gastrin: obligatory intermediate in the postprandial mobilization of gastric histamine in the rat.

In unoperated fasted rats, feeding raised the serum gastrin concentration, reduced the gastric mucosal histamine content and activated the gastric histidine decarboxylase. The reduction of gastric histamine and activation of histidine decarboxylase was induced also by the injection of pentagastrin. In antrectomized rats, feeding failed to produce these effects. Injection of pentagastrin, however, still lowered gastric histamine and activated gastric histidine decarboxylase. Thus, antral gastrin seems to be an obligatory mediator of the postprandial activation of histidine decarboxylase and mobilization of histamine.

Suppression of rat stomach histidine decarboxylase activity by histamine: H2-receptor-mediated feed-back.

1. Gastrin activates rat stomach histidine decarboxylase. Exogenous histamine suppressed the basal enzyme activity in unoperated, in nephrectomized, in vagally denervated and in antrectomized rats, and counteracted the pentagastrin-induced enzyme activation in unoperated rats.2. Kinetic analysis of enzyme-catalysed histidine decarboxylation in extracts from untreated vagotomized and from histamine-treated vagotomized rats showed that the histamine-induced suppression of histidine decarboxylase activity probably reflects a reduced enzyme concentration. Moreover, the enzyme half-life in vagotomized rats after treatment with histamine was shorter than the half-life observed after inhibition of enzyme synthesis. These observations suggest that administration of histamine not only inhibits enzyme synthesis but also causes an accelerated rate of elimination of histidine decarboxylase.3. Intravenous infusion of histamine caused marked displacement of the pentagastrin dose-response curve, in a manner suggesting a reduced sensitivity to pentagastrin.4. After H(2)-receptor blockade, but not after H(1)-receptor blockade, histamine was less effective in suppressing the enzyme activity. Furthermore, H(2)-receptor blockade augmented the pentagastrin-induced enzyme activation.5. The results suggest that histamine (via H(2)-receptors) reduces the sensitivity of the histamine-storing cells to gastrin and that H(2)-receptor blockade induces the opposite effects.6. We propose that the histamine-storing cells in the rat stomach are endowed with H(2)-receptors and that exogenous histamine is capable of acting directly on the histamine cells. This may reflect a physiological control mechanism whereby mobilized endogenous histamine modifies its own synthesis and release.

Stereological Changes in Rat Parietal Cells After Vagotomy and Antrectomy

Gastric parietal cells from 44 male adult Sprague-Dawley rats were studied in the electron microscope. The animals were divided into seven groups: normal fasted, normal nonfasted, 4 weeks after vagotomy, 10 weeks after vagotomy and pyloroplasty, 10 weeks after pyloroplasty, 4 weeks after antrectomy, and 10 weeks after antrectomy. Stereological data were obtained from 30 to 40 parietal cells in each animal. In the normal nonfasted rats the parietal cells high up in the glands had a larger secretory surface density than those at deeper levels of the mucosa. Neck parietal cells containing a few mucous granules constituted about 10% of the total number of parietal cells in the normal rats; they were most common in the midgland region. The average parietal cell volume in the normal fasted rats was calculated to be 1100 mu3; the cells were significantly smaller 10 weeks after vagotomy and pyloroplasty and still smaller 10 weeks after antrectomy. In this respect the results after vagotomy and pyloroplasty did not differ from those after pyloroplasty alone. The parietal cell density in the normal fasted rats averaged 144 X 10(3) cells per mm3; in the operated rats (except for the 4-week vagotomized rats) the cells became more numerous. The parietal cell volume density was about equal in all groups of animals, except for the 10-week antrectomized rats, where a significant reduction occurred.

Is the basal activity of rat stomach histidine decarboxylase affected by antrectomy?

The serum gastrin concentration and the gastric histidine decarboxylase activity are high in freely fed, unoperated rats but low in antrectomized rats. Following food deprivation the serum gastrin level and the enzyme activity are reduced simultaneously in the unoperated rats. After fasting for 36-48 h - but not before - the enzyme activity drops to the same low levels as in antrectomized rats.

Alterations in secretory patterns following antrectomy in rats with Pavlov pouches.

1. In conscious rats provided with Pavlov pouches, with the antrum retained or resected,the gastric secretory response to various stimuli has been studied. Each acid secretory response was related to that obtained with maximal doses of methacholine and histamine in combination, presumed to reflect the maximal secretory capacity of the mucosa. 2. Three weeks after the operation, the maximal acid secretory capacity was 60 percent lower in the antrectomized than in the intact Pavlov pouch rats; the difference was still larger at 6 weeks and 3-5 months, owing to a gradual increase in the rats with the antrum retained. 3. Antrectomy reduced interdigestive secretion of acid to the same degree as the concomitant reduction in maximal secretory capacity. 4. Acid secretion in response to a maximal infusion of pentagastrin was reduced by about 50 percent at 3 and about 65 percent at 6 weeks after antrectomy. No significant difference was, however, noted between the antrectomized and intact rats when the responses were related to the maximal secretory capacity. The dose response curve to pentagastrin revealed a redcued responsiveness to submaximal doses of this agent following antrectomy. 5. The maximal acid secretory response to histamine was reduced after antrectomy, although the sensitivity to submaximal infusions of histamine appeared to be increased. 6. The mean secretroy output to 2-deoxy-D-glucose was reduced by about 65 percent and that to food by about 85 percent following antrectomy. 7. After antrectomy a background infusion of pentagastrin enhanced the secretory responses to 2-deoxy-D-glucose and to food but did not restore the responses to the levels in the intact rats. The feeding responses as related to the maximal secretory capacity were, however, similar in the two groups on infusing pentagastrin in the antrectomized rats. 8. Interdigestive secretion of pepsin was reduced by about 60 percent after antrectomy, while the peak response to 2-deoxy-Dglucose was about twice the interdigestive level in both groups. Pepsin secretion in response to food showed an increased secretion above the interdigestive level of longer duration in the antrectomized than in the intact Pavlov pouch rats. 9. The irreversibily reduced responsiveness of the gastric mucosa after antrectomy is discussed in relation to known morphological and biochemical changes.