Multiple Carcinoid Tumors of the Stomach with Hypergastrinemia

A 42-yr-old woman presented with multiple carcinoid tumors in her stomach and a markedly elevated serum gastrin level. Total gastrectomy was performed, and 22 small carcinoid tumors were found in the gastric fundus and body. A high serum gastrin level was revealed in the gastric drainage veins; still more gastrin was detected in the carcinoid tumors by the immunohistochemical method, and many secretory granules were found in the tumor cells with an electron microscope. The fundic gland showed marked atrophy, and there was some conglobation of endocrine cells (ECL cells). This case suggests a hypothetic sequence of anacidity due to atrophic gastritis----hypergastrinemia----proliferation of ECL cells----multiple carcinoids. A search of the Japanese literature revealed that 26 cases of multiple carcinoid tumors in the stomach have been reported so far, and most of them support this hypothesis.     

Long-term omeprazole treatment suppresses body weight gain and bone mineralization in young male rats

BACKGROUND: The stomach is rich in endocrine cells, including those producing ghrelin, which is thought to play a role in the control of body growth. Omeprazole treatment is associated with hypergastrinaemia, resulting in growth of the oxyntic mucosa in general and the enterochromaffin-like (ECL) cells in particular. In the present study, we examined the effects of long-term omeprazole treatment on young male rats with respect to body growth and stomach. METHODS: Male rats (24 days old) were treated with omeprazole (400 micromol/kg/day) or vehicle for 77 days. The body weight was recorded twice per week. At sacrifice, dual-energy X-ray absorptiometry (DXA) was used to assess total bone area, bone mineral content (BMC), bone mineral density (BMD) and body composition (fat and lean body mass). The lengths of the spine and the femur were recorded. The plasma concentrations of gastrin and histamine were determined by radioimmunoassays. The endocrine cells of the stomach were examined by immunocytochemistry. RESULTS: The body weight gain was suppressed by omeprazole treatment. The bone area, BMC and BMD were reduced, while the lengths of the spine and the femur and the body composition were unchanged. Omeprazole-induced hypergastrinaemia was associated with enlargement of the oxyntic area and with hyperplasia of ECL cells but not of A-like cells and D cells. In contrast, the enterchromaffin (EC) cell density in the antrum was reduced. CONCLUSIONS: Omeprazole treatment of young male rats reduces body weight and bone mass gain. The densities of ECL cells in the oxyntic mucosa was increased and of the EC cells in the antral mucosa reduced.     

Long-term Omeprazole Treatment Suppresses Body Weight Gain and Bone Mineralization in Young Male Rats

Background: The stomach is rich in endocrine cells, including those producing ghrelin, which is thought to play a role in the control of body growth. Omeprazole treatment is associated with hypergastrinaemia, resulting in growth of the oxyntic mucosa in general and the enterochromaffin-like (ECL) cells in particular. In the present study, we examined the effects of long-term omeprazole treatment on young male rats with respect to body growth and stomach. Methods: Male rats (24 days old) were treated with omeprazole (400 µmol/kg/day) or vehicle for 77 days. The body weight was recorded twice per week. At sacrifice, dual-energy X-ray absorptiometry (DXA) was used to assess total bone area, bone mineral content (BMC), bone mineral density (BMD) and body composition (fat and lean body mass). The lengths of the spine and the femur were recorded. The plasma concentrations of gastrin and histamine were determined by radioimmunoassays. The endocrine cells of the stomach were examined by immunocytochemistry. Results: The body weight gain was suppressed by omeprazole treatment. The bone area, BMC and BMD were reduced, while the lengths of the spine and the femur and the body composition were unchanged. Omeprazole-induced hypergastrinaemia was associated with enlargement of the oxyntic area and with hyperplasia of ECL cells but not of A-like cells and D cells. In contrast, the enterchromaffin (EC) cell density in the antrum was reduced. Conclusions: Omeprazole treatment of young male rats reduces body weight and bone mass gain. The densities of ECL cells in the oxyntic mucosa was increased and of the EC cells in the antral mucosa reduced.     

Effects of calcium deficiency and calcium supplementation on gastrectomy-induced osteopenia in the young male rat

BACKGROUND: Surgical removal of the stomach (gastrectomy, Gx) induces osteopenia. In this study we compared the osteopenic effect of Gx with that induced by calcium (Ca) deficiency. METHODS: Young male rats were subjected to Gx and/or low Ca diet (-Ca). A group of Gx rats received standard diet + oral Ca supplementation (+Ca). The rats were killed at various times after the operation/start of treatment (longest time 12 weeks). After 8 weeks on low Ca diet, the blood Ca2+ concentration was lowered slightly in both Sham-operated and Gx rats. The calvariae were subjected to transillumination analysis and quantitative histomorphometry. Also the tibiae were subjected to histomorphometry. RESULTS: Transillumination of the calvariae revealed extensive bone loss in the rats that had been subjected to Gx and/or low Ca diet. Gx + Ca induced the same bone loss as Gx alone. These observations were later confirmed in quantitative terms by histomorphometry (Sham-Ca 56%, Gx 35%, Gx + Ca 32%, Gx - Ca 58% less bone area than in Sham). The osteopenia induced by Gx + low Ca diet seetned more rapid in onset than that induced by Gx or low Ca diet alone. Tibiae from Gx rats and rats given a low Ca diet displayed a reduced trabecular bone volume (Sham-Ca 27% remaining, Gx 36%, Gx + Ca 44%, Gx - Ca 17%) and reduced trabecular number (Sham-Ca 44% remaining, Gx 41%, Gx + Ca 56%, Gx - Ca 33%). The trabecular thickness was reduced in the Gx rats and Gx - Ca rats (Gx 78% remaining, Gx - Ca 63%) but not in Sham-operated rats receiving a low Ca-diet (95% remaining). CONCLUSION: Although the pattern of osteopenia was qualitatively quite similar in Gx rats and Ca-deficient rats, in quantitative terms the low Ca diet was more detrimental to bone than Gx. Ca deficiency induced a similar degree of osteopenia in both Sham and Gx rats. Ca supplementation failed to prevent the Gx-induced osteopenia.     

Unilateral vagal denervation suppresses omeprazole-induced trophic effects on the denervated side of the rat stomach.

In several experimental animals treatment with large doses of the proton pump inhibitor omeprazole leads to hypergastrinemia and with time to trophic effects in the acid-producing part of the stomach, most notably an increased density of the histamine-producing enterochromaffin-like (ECL) cells. The trophic effects are thought to reflect the increase in circulating gastrin. In the present study unilateral vagal denervation in the rat partly suppressed the tropic effects seen in the denervated side of the stomach but not those in the intact side after treatment with omeprazole for 10 weeks. Unilateral vagal denervation significantly reduced the proliferative stimulus of omeprazole on the ECL cells in the denervated part of the stomach. Thus, an intact vagal innervation appears to be essential for the capacity of the oxyntic mucosa, including the ECL cells, to respond to elevations in serum gastrin. We suggest that gastrin and the vagus interact to maintain trophic control of the oxyntic glands.     

Histamine as an intermediate growth factor in genesis of gastric ECLomas associated with hypergastrinemia in mastomys

Profound and sustained inhibition of gastric acid secretion has been associated with development of carcinoid tumors of the fundic enterochromaffin-like (ECL) cells in rodents. While ECL cell hyperplasia has been recognized in humans, the development of carcinoid tumors is rare and often confined to patients under treatment for gastrinoma related to the multiple endocrine neoplasia type I (MEN1) syndrome. The Mastomys was utilized as a model for the rapid induction of ECLomas by insurmountable acid secretory blockade induced by the pharmacologically irreversible H₂-receptor antagonist, loxtidine. Loxtidine-induced ECL cell hyperplasia and neoplasia were compared in the absence of presence of cyproheptadine (0.5 mg/kg), an H₁-receptor antagonist. Loxtidine administration resulted in a significant increase in ECL cell hyperplasia and neoplasia as well as an increase in ECL cell number, mucosal thickness, plasma gastrin levels, and stomach weight. Cyproheptadine ameliorated loxtidine-induced ECL cell hyperplasia and neoplasia and significantly decreased loxtidine-stimulated increases in ECL cell number. Nevertheless, cyproheptadine failed to alter the loxtid-ineinduced increase in plasma gastrin, stomach weight or mucosal height. The results indicate that cyproheptadine, an H₁-receptor antagonist, inhibits loxtidine-induced ECL cell hyperplasia independent of any effects on serum gastrin.     

Zinc in total parenteral nutrition: requirements and metabolic effects.

Rat gastric oxyntic glands contain argyrophil "enterochromaffin-like" endocrine cells that synthesize and store histamine and also have APUD ability--they can take up exogenous L-5-hydroxytryptophan (5-HTP), can decarboxylate it to 5-hydroxytryptamine (5-HT, serotonin) by the enzyme DOPA-decarboxylase, and can store the amine. Previous cytochemical studies suggested that these cells correspond to both the ECL and A-like cells, the two predominant endocrine cells identified by electron microscopy (EM) in rat oxyntic glands. In a recent study, however, we demonstrated that the ECL but not the A-like cell exhibited APUD ability when rat gastric mucosa was incubated with H3-5-HTP and studied by EM radioautography. The purpose of the present study was to identify by EM radioautography the histamine-synthesizing endocrine cells in the rat stomach. Pieces of rat (male Sprague-Dawley) gastric mucosa were incubated in organ culture with L-H3-histidine (50 muCi, 1.8 x 10(-5) M) with and without inhibitors and were processed for LM and EM radioautography. H3-histidine labeled the ECL cells heavily but the A-like and other endocrine cells only lightly. The labeling of ECL cells was only modestly reduced by cycloheximide, an inhibitor of protein synthesis, whereas the labeling of A-like and other endocrine cells was almost abolished. In contrast, the labeling of ECL cells was markedly reduced by 4-bromo-3-hydroxybenzyloxyamine (NSD-1055), an inhibitor of histidine decarboxylase and DOPA decarboxylase, but was not appreciably affected by carbidopa, an inhibitor of only the DOPA decarboxylase. Incubations with H3-histamine (50 muCi, 0.9 x 10(-5) M) failed to label endocrine cells. Thus, this study demonstrates that the ECL but not the A-like cell is the histamine-synthesizing endocrine cell of the rat stomach.     

Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans

Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by light and electron microscopic immunohistochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previously been clarified. The localization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, we determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.     

Dietary α-ketoglutarate reduces gastrectomy-evoked loss of calvaria and trabecular bone in female rats

Objective. Surgical removal of the stomach (gastrectomy, Gx) leads to osteopenia in animals and in humans. In the rat, Gx adversely affects calvaria and trabecular bone. α-Ketoglutarate (AKG) is a precursor of hydroxyproline – the most abundant amino acid in bone collagen. The purpose of this study was to investigate the effects of dietary AKG on Gx-induced osteopenia. Material and methods. Twenty female Sprague-Dawley rats were subjected to Gx and divided between two groups: Gx+AKG in the drinking water and Gx+Vehicle (i.e. drinking water without AKG). Another 20 rats were sham-operated and divided between two groups: Sham+AKG and Sham+Vehicle. The daily dose of AKG was 0.43 g per 100 g rat. All the rats were killed 8 weeks later and the calvariae, femora and tibiae were collected. The integrity of the calvariae was analysed planimetrically, following transillumination and photography. The bone mineral content (BMC) and bone mineral density (BMD) were measured in the right femorae and tibiae (bone densitometry), leaving the left femorae and tibiae to be analysed histomorphometrically (measurement of trabecular bone volume and trabecular fractal dimension). Results. Gx caused calvarial bone degradation, reduced trabecular bone (femur and tibia) and impaired trabecular architecture. In addition, Gx lowered the femoral/tibial BMC and BMD (mainly cortical bone). Dietary AKG counteracted the Gx-evoked impairment of calvaria and trabecular bone but failed to affect the BMC and the BMD in either sham- operated or Gx rats. Conclusions. Gx resulted in loss of calvarial, trabecular and cortical bone in the rat. AKG counteracted the effect of Gx on calvaria and trabecular bone but not on cortical bone.     

Effects of partial resection of acid-secreting mucosa on plasma gastrin and enterochromaffin-like cells in the rat stomach

Female rats were subjected to various degrees (50, 75, 90 and 100%) of fundectomy, i.e. resection of the acid-producing part of the stomach, to compare the effects of different degrees of reduction of the amount of acid reaching the antrum. Plasma gastrin was monitored for 10 weeks after the operation. Histidine decarboxylase (HDC) activity, histamine concentration and density of enterochromaffin-like (ECL) cells in the remaining oxyntic mucosa were determined in the rats subjected to 50 or 75% fundectomy. There was a close correlation between the amount of acid-producing mucosa removed and the plasma gastrin levels, the highest gastrin level being observed in the rats subjected to 100% fundectomy. HDC activity, histamine concentration and ECL cell density seemed to reflect plasma gastrin concentration. These findings indicate that hypergastrinemia induced by surgical removal of acid-producing mucosa in the rat has the same effects on oxyntical mucosal HDC activity, histamine concentration and ECL cell density as hypergastrinemia induced by continuous gastrin infusion or by long-term treatment with effective antisecretagogues.     

Effects of gastrin on calcium homeostasis in chickens

As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) were found to lower the blood Ca2+ concentration in the chicken. Furthermore, gastrin enhanced the uptake of 45Ca into the femur. It has been suggested previously that gastrin causes hypocalcemia in the rat by releasing gastrocalcin, a hypothetical hormone thought to reside in the acid-producing part of the stomach. The results of the present study in the chicken are in agreement with this concept. Not only exogenous, but also endogenous gastrin lowered blood calcium levels. Thus, the serum gastrin concentration was increased in response to ranitidine-evoked blockade of the gastric acid output; the rise in gastrin was associated with a transient drop in blood calcium. Also, food intake produced a rise in the serum gastrin concentration and a transient drop in blood calcium. However, injection of ranitidine or food intake in proventriclectomized (acid-producing part of the stomach extirpated) chickens failed to lower blood calcium, supporting the view that the gastrin-evoked hypocalcemia depends upon an agent in the gastric (proventriculus) mucosa. We suggest that endogenous and exogenous gastrin evoke hypocalcemia in the chicken by the same mechanism as that which has been postulated in the rat, i.e. by mobilization of the candidate hormone gastrocalcin from endocrine cells in the acid-producing gastric mucosa.     

Endocrine cells in the human oxyntic mucosa. A histochemical study

The oxyntic mucosa of the human stomach harbors at least five different endocrine cell types (ECL cells, A-like or X cells, somatostatin cells (D), enterochromaffin (EC) cells, and D1 or P cells). Little is known about their functional roles, and of the hormones they produce only somatostatin has been identified. The relative frequency and regional distribution of the different endocrine cell populations were studied in 13 adults with no manifest gastrointestinal disease. From each of them at least three biopsy specimens were taken at seven fixed locations within the oxyntic mucosa. The specimens were examined for the different endocrine cell types by means of immunocytochemistry (staining with antisera against chromogranin A,5-hydroxytryptamine, and somatostatin) and silver staining techniques (demonstration of argyrophil cells by the methods of Grimelius or Sevier-Munger). Chromogranin-positive cells included all endocrine cells identified by the other staining techniques. Grimelius-positive cells included all endocrine cells except the somatostatin cells. Sevier-Munger-positive cells, finally, included the ECL cells and the EC cells. The frequency of ECL cells could be calculated by subtracting the number of EC cells from the number of Sevier-Munger-positive cells. The ECL cells represented 35% of the total endocrine number, somatostatin cells 26%, and EC cells 25%. The remaining 14% consisted of A-like cells, D1 cells, and P cells. Generally, the endocrine cells predominated in the basal portion of the glands, but the various populations of endocrine cells were not uniformly distributed in the various regions of the oxyntic mucosa. However, representative specimens could be obtained from the main body of the stomach, and the results indicate that the examination of a fairly small number of specimens from the main body of the stomach may be sufficient for assessing the frequency of endocrine cells in the oxyntic mucosa of individual patients.     

Relations between circulating gastrin and endocrine cell proliferation in the atrophic gastric fundic mucosa

It has been suggested that gastrin may be a causative factor in the proliferation of gastric fundic mucosal endocrine cells, as seen in the Zollinger-Ellison syndrome and in atrophic gastritis with hypergastrinemia of antral origin. In the present study, morphometrically determined densities of endocrine cells in fundic mucosal biopsy specimens were related to basal levels of serum gastrin in 10 normal controls and 60 patients with achlorhydric fundic atrophic gastritis, of which 45 had pernicious anemia (5 with fundic mucosal carcinoid) and 15 had atrophic gastritis without pernicious anemia. The densities of fundic mucosal endocrine cells were positively related to the levels of serum gastrin (atrophic gastritis, rs = 0.65; atrophic gastritis and normal controls, rs = 0.72). The highest levels of serum gastrin were found in patients with carcinoid tumors (mean, 1659.3 pmol/l), followed by those in patients with focal hyperplasias (cluster formation) of endocrine cells (mean, 503.2 pmol/l) and those in patients without focal hyperplasias (mean, 304.4 pmol/l) (p = 0.03 and p = 0.04, respectively).     

Identification of somatostatin and gastrin receptors on enterochromaffin-like cells from Mastomys gastric tumors.

Histamine-secreting enterochromaffin-like (ECL) cells of the gastric fundus of the Mastomys can develop into solid ECL cell tumors, either spontaneously or after induction by acid inhibition. We used this tumor tissue to perform in vitro receptor autoradiography for somatostatin (SS), gastrin, and substance-P, using, respectively, [125I]Tyr3-octreotide, [125I]gastrin-17, and [125I]Bolton-Hunter-labeled substance-P as radioligands. A high density of SS receptors was found in the nontumor fundic mucosa, where gastrin receptors were only barely detectable. However, in the group of spontaneously developing ECL cell tumors, a high density of SS and gastrin receptors was observed, homogeneously distributed in the tumor tissue. In addition, the loxtidine-induced ECL cell tumors expressed a high density of SS and gastrin receptors. The receptors were specific for the respective peptide and of high affinity, with a dissociation constant (Kd) of 0.90 nM for SS receptor and 0.87 nM for gastrin receptors. No substance-P receptors were detected on the ECL cell tumors, although they were present in the muscle layers of the Mastomys gastric fundus. These results demonstrate that ECL-derived tumors express receptors for both SS and gastrin. This observation is consistent with the proposal that there is substantial regulation of the histamine-producing ECL cell by SS and gastrin. The presence of gastrin receptors is compatible with a role for gastrin as a trophic factor in ECL cell hyperplasia and neoplasia. The expression of SS receptors may be of diagnostic and therapeutic relevance in the regulation of ECL function and neoplastic transformation.     

Proliferation of enterochromaffinlike cells in omeprazole-treated hypergastrinemic rats

The effect of high doses of omeprazole on the proliferation of the histamine-storing endocrine cells in the oxyntic mucosa, the so-called enterochromaffinlike (ECL) cells, was studied in the rat stomach by combining immunocytochemical staining for histamine with autoradiography after in vivo labeling with [3H]thymidine. Under basal conditions the ECL cells divided very slowly. A progressive increase in the ECL cell labeling index was observed from the second day of omeprazole treatment. The ECL cell density increased progressively from the ninth day of treatment. The plasma gastrin levels were doubled and the labeling index of the cells in the progenitor cell zone was significantly increased. Our data indicate that the omeprazole-evoked ECL cell hyperplasia is a result of accelerated self-replication. The positive correlation between the plasma gastrin concentration and the ECL cell labeling index is compatible with a causal relationship between circulating gastrin levels and increased ECL cell density.     

High gastrin cell activity and low ghrelin cell activity in high-anxiety Wistar Kyoto rats

Ghrelin is produced by gastric A-like cells and released in response to food deprivation. Interestingly, psychological stress also raises circulating ghrelin levels. This study compared plasma ghrelin levels in Sprague-Dawley (SPD) rats and high-anxiety Wistar Kyoto (WKY) rats. The two strains were also compared with respect to plasma gastrin, a gastric hormone with a pre- and postprandial release pattern opposite to that of ghrelin, and to the activity of the gastrin-dependent, histamine-forming ECL cells in the gastric mucosa. The rats were killed after being freely fed or after an over-night fast. The stomachs were weighed and tissue samples were collected for histological and biochemical analysis. Plasma ghrelin and gastrin levels were determined by RIA. While fasted SPD rats had higher plasma ghrelin levels than fasted WKY rats (P < 0.001), plasma ghrelin did not differ between freely fed rats of the two strains. Gastrin levels were higher in fed WKY rats than in fed SPD rats (P < 0.001). Despite the higher plasma gastrin level, the oxyntic mucosal histidine decarboxylase (HDC) activity (a marker of ECL-cell activity) in fed rats and the mucosal thickness did not differ between the two strains. In a subsequent study, rats were subjected to water-avoidance stress for 60 min, causing plasma gastrin to increase in WKY rats (P < 0.001) but not in SPD rats. In conclusion, high-anxiety WKY rats had lower circulating ghrelin and higher gastrin than SPD rats in both the fasted and fed state, while the ECL-cell activity (HDC activity) was only moderately affected.     

Gastrectomized rats respond with exaggerated hypercalcemia to oral and intravenous calcium loads because of impaired ability of bone to take up Ca2+

BACKGROUND: Gastrectomy (Gx) causes osteopenia. The hypothesis tested in the present study is that Gx affects Ca homeostasis and that an impaired ability to handle Ca contributes to the Gx-evoked osteopenia. METHODS: SHAM-operated and Gx rats were compared with respect to changes in blood Ca2+ after oral or intravenous loads of CaCl2 1-2 weeks or 2-4 months after the operations. RESULTS: Different doses of oral CaCl2 raised blood Ca2+ more in Gx than in SHAM rats, more so after 2-4 months than after 1-2 weeks. The rise was greater in fasted (48 h) rats than in fed rats regardless of whether they were SHAM or Gx. While SHAM rats tolerated high doses of CaCl2 well, Gx rats died when exposed to quite modest doses, particularly 2-4 months after Gx. Intravenous infusion of CaCl2 (2,500 micromol/kg/h) induced a greater and steeper rise in blood Ca2+ in Gx rats than in SHAM rats. Kinetic analysis of the blood Ca2+ data showed Gx rats to display: 1) a decreased Ca2+ elimination clearance from the central distribution compartment (blood), 2) a reduced size of the peripheral distribution compartment (the so-called bone fluid compartment). and 3) a spectacular decrease in the intercompartmental clearance (transfer of Ca2+ from blood to bone). These effects were notably apparent after 2-4 months. At sacrifice, the Gx-evoked osteopenia was confirmed by planimetric analysis of the calvariae. revealing 40% reduction of bone tissue after 2-4 months. CONCLUSIONS: Based on the present data we argue that Gx rats respond with exaggerated hypercalcemia to oral and intravenous CaCl2 loads because of a greatly impaired transfer of Ca+ from blood to bone. We suggest that with time this impairment results in osteopenia.     

Regulation of food intake: The gastric X/A-like endocrine cell in the spotlight

Nutritional status influences hormone secretion from specialized enteroendocrine cells within the gut mucosa. These hormones regulate food intake by mediating information to central neurocircuitries in the brainstem and forebrain (eg, hypothalamic nuclei). Intestinal enteroendocrine cells were believed to be the main source of gut peptides regulating food intake. However, recent evidence highlights a specific endocrine cell within the oxyntic glands of the stomach as an important player in appetite control. Acylated ghrelin is the only known orexigenic hormone peripherally produced in gastric X/A-like cells and centrally acting to stimulate food intake. Recent advances led to the assumption that des-acylated ghrelin, coreleased with acylated ghrelin, is also involved in regulating food intake. This, and the novel observation that nesfatin-1, which inhibits food intake, is expressed in ghrelin-producing cells of the stomach, supports an important role for gastric X/A-like cells in regulating food intake. Another peptide, obestatin, was initially described as a ghrelin gene product inhibiting food intake, but subsequent studies produced controversial data and its action as an anorexic factor is doubtful. Importantly, synergistic interactions between ghrelin and intestinal peptides seem to orchestrate food intake and body weight regulation, which may have implications for understanding mechanisms leading to the treatment of obesity.     

胃促生长素与消化道运动

胃促生长素(ghrelin)是新发现的内源性多肽,有促生长激素分泌和调节食欲、调节能量代谢的作用,它主要由胃底X/A样细胞分泌,广泛分布于胃和肠道组织,且与胃动素在结构上有高度相同性,故其与消化道运动的关系近来备受关注,现综合有关文献,对ghrelin与消化道运动的关系作一综述.     

Antrectomy does not accelerate reversal of omeprazole-induced trophic effects in the rat stomach.

The oxyntic mucosa in the rat stomach is under the influence of circulating gastrin. The histamine-producing enterochromaffin-like (ECL) cells constitute the major endocrine cell population in the oxyntic mucosa. They are notably sensitive to changes in the serum gastrin concentration and respond to long-term hypergastrinemia with hyperplasia, whereas hypogastrinemia induces hypoplasia. In the present study long-term, sustained hypergastrinemia was induced by daily treatment with a high dose of the proton pump inhibitor omeprazole. After 10 weeks omeprazole-treated and control rats were antrectomized, resulting in prompt hypogastrinemia. Antrectomy was followed by a rapid reduction of the thickness of the oxyntic mucosa and a somewhat slower reduction of the ECL cell number in both omeprazole-treated and control rats. The percentage decrease in the ECL cell number with time was similar in both groups; after 2-3 weeks the ECL cell number was half of that before antrectomy in both groups. Interestingly, however, 12 weeks after antrectomy the ECL cell number in the omeprazole-pretreated rats remained elevated compared with untreated rats. The histamine concentration of the oxyntic mucosa was markedly lowered within a week after antrectomy in both omeprazole-treated and control rats. Although antrectomy induces hypogastrinemia and although atrophy develops rapidly in the oxyntic mucosa, the omeprazole-induced ECL cell hyperplasia was not completely reversed by antrectomy during the 12 weeks of examination.