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C M Zhao

Publications and source records attributed to C M Zhao.

At least 19 recordsLinked to original sources
PubMed2001

A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control.

Ghrelin is a 28 a.a. gastric peptide, recently identified as a natural ligand of the growth hormone secretagogue receptor (orphan receptor distinct from the receptor for growth hormone releasing hormone). In the present study, radioimmunoassay demonstrated ghrelin-like material in the rat oxyntic mucosa with moderate amounts also in antrum and duodenum. Small amounts were found in the distal intestines and pancreas. Northern blot analysis revealed abundant ghrelin mRNA in the oxyntic mucosa. Immunocytochemistry demonstrated ghrelin-immunoreactivity in endocrine-like cells in the oxyntic mucosa. Such cells occurred in low numbers also in the antrum and duodenum. The rat oxyntic mucosa is rich in endocrine (chromogranin A/pancreastatin-immunoreactive) cells, such as the histamine-rich ECL cells (65-75% of the endocrine cells), the A-like cells (20-25%) and the D cells (somatostatin cells) (10%). The ghrelin-immunoreactive (IR) cells contained pancreastatin but differed from ECL cells and D cells by being devoid of histamine-forming enzyme (ECL cell constituent) and somatostatin (D cell constituent). Hence, ghrelin seems to occur in the A-like cells. The ghrelin-IR cells in the antrum were distinct from the gastrin cells, the serotonin-containing enterochromaffin cells and the D cells. Conceivably, ghrelin cells in the antrum and distally in the intestines also belong to the A-like cell population. The concentration of ghrelin in the circulation was lowered by about 80% following the surgical removal of the acid-producing part of the stomach in line with the view that the oxyntic mucosa is the major source of ghrelin. The serum ghrelin concentration was higher in fasted rats than in fed rats; it was reduced upon re-feeding and seemed unaffected by 1-week treatment with the proton pump inhibitor omeprazole, resulting in elevated serum gastrin concentration. Infusion of gastrin-17 for 2 days failed to raise the serum ghrelin concentration. Omeprazole treatment for 10 weeks raised the level of HDC mRNA but not that of ghrelin mRNA or somatostatin mRNA in the oxyntic mucosa. Hence, unlike the ECL cells, ghrelin-containing A-like cells do not seem to operate under gastrin control.

Animals↗
PubMed2001

Functionally impaired, hypertrophic ECL cells accumulate vacuoles and lipofuscin bodies. An ultrastructural study of ECL cells isolated from hypergastrinemic rats.

ECL cells in the oxyntic mucosa of stomach control gastric acid secretion by mobilizing histamine in response to gastrin. They respond to gastrin also with hypertrophy and hyperplasia. ECL cells exhibit functional impairment upon long-term gastrin stimulation. The impairment is manifested in a gradual decline of the activity of the histamine-forming enzyme per individual ECL cell and in a failure of gastrin to mobilize histamine. The mechanism behind this impairment is unknown. In the present study, rats were treated with the proton pump inhibitor pantoprazole for 45 days to induce sustained hypergastrinemia. The ECL cells were isolated from normogastrinemic and hypergastrinemic rats and size-separated from other mucosal cells by the elutriation technique. The total ECL cell number was twofold higher in hypergastrinemic rats than in normogastrinemic rats, and most of the cells appeared in elutriation fractions where large cells predominate. The ECL cells of the different fractions were analyzed by quantitative electron microscopy. Normal-sized ECL cells from hypergastrinemic rats displayed a reduced number of secretory vesicles (probably because of degranulation) compared with normal-sized ECL cells from normogastrinemic rats. Hypertrophic ECL cells from hypergastrinemic rats had an unchanged number of secretory vesicles, supporting the view that such cells fail to respond to gastrin with degranulation. Although both normal-sized and hypertrophic ECL cells from hypergastrinemic rats contained vacuoles, those in the hypertrophic ECL cells were larger and more numerous. In addition, hypertrophic ECL cells were found to contain numerous, prominent lipofuscin bodies which are the presumed end product of crinophagia. Conceivably therefore, large vacuoles and lipofuscin bodies cause functional impairment of the hypertrophic ECL cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

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.

Age Factors↗
PubMed2001

Effects of CCK2 receptor blockade on growth parameters in gastrointestinal tract and pancreas in rats.

Gastrin has a growth-promoting effect on the oxyntic mucosa of the stomach but has been claimed also to affect other parts of the gastrointestinal tract and pancreas. This report describes the effects of the cholecystokinin, (CCK2) receptor antagonists YM022 and YF476 on various growth parameters in the gastrointestinal tract and pancreas of the rat. YM022 and YF476 were given subcutaneously in doses known to produce maximum and sustained CCK2 receptor blockade. The body weight was not affected. However, the oxyntic mucosal weight, thickness and protein and DNA contents were reduced by 15-20% already within 1-2 days and by about 30% after 4-8 weeks of CCK2 receptor blockade. Hence, the response of the oxyntic mucosa to CCK2 receptor blockade was in the form of hypotrophy (reduced protein content) and hypoplasia (reduced DNA content). There were no obvious effects of CCK2 receptor blockade on the intestine or pancreas (nor on liver, kidney or thyroid). The proton pump inhibitor omeprazole was used to induce hypergastrinaemia and was given with or without YM022. Omeprazole treatment for 4 weeks increased the oxyntic mucosal weight and thickness by 15-20%. YM022 prevented these effects. We conclude that while elevated circulating gastrin levels, acting on CCK2 receptors, exert a growth-promoting effect on the oxyntic mucosa (but not elsewhere), normal serum gastrin levels exert a mucosa-preserving effect.

Animals↗
PubMed2001

Are current textbooks good enough for physiology education? For example, the ECL cells are missing.

Current textbooks are believed to provide an updated knowledge. Medical students usually read the textbooks but not the literature that contain the original research articles and reviews. Here, we examined the gap between the current textbooks and literature with the enterochromaffin-like (ECL) cells as an example. A total of 70 textbooks that were published for medical education during the last 10 yr was examined. The literature has been searched mainly from the Internet. We found that most textbooks (59 of 70) fail to mention the ECL cells. Due to the lack of information on the ECL cells, the mechanisms behind gastric acid secretion are described variously from book to book. However, up to the year 2000, 574 research articles and reviews have been published on the various aspects of the ECL cells. The role of the ECL cells in the regulation of the acid secretion has been well demonstrated for more than 20 years. The fact that the textbooks are out of date cannot be explained by the time required to write and publish them. Therefore, we question whether or not the current textbooks are good enough for physiology education and suggest both teachers and students read not only the textbooks, but also utilize the other sources such as the Internet to find and fill the gaps between the textbooks and literature. This is one of the approaches of problem-based learning.

Enterochromaffin-like Cells↗
PubMed2000

Effect of cholecystokinin-2 receptor blockade on rat stomach ECL cells. A histochemical, electron-microscopic and chemical study.

The ECL cells in the oxyntic mucosa of rat stomach produce histamine and chromogranin A-derived peptides such as pancreastatin. The cells respond to gastrin via cholecystokinin-2 (CCK2) receptors. A CCK2 receptor blockade was induced by treatment (for up to 8 weeks) with two receptor antagonists, YM022 and YF476. Changes in ECL-cell morphology were examined by immunocytochemistry and electron microscopy, while changes in ECL cell-related biochemical parameters were monitored by measuring serum pancreastatin and oxyntic mucosal pancreastatin, and histamine concentrations, and histidine decarboxylase (HDC) activity. The CCK2 receptor blockade reduced the ECL-cell density only marginally, if at all, but transformed the ECL cells from slender, elongated cells with prominent projections to small, spherical cells without projections. The Golgi complex and the rough endoplasmic reticulum were diminished. Secretory vesicles were greatly reduced in volume density in the trans Golgi area. Circulating pancreastatin concentration and oxyntic mucosal HDC activity were lowered within a few hours. Oxyntic mucosal histamine and pancreastatin concentrations were reduced only gradually. The CCK2 receptor blockade was found to prevent the effects of omeprazole-evoked hypergastrinaemia on the ECL-cell activity and density. In conclusion, gastrin, acting on CCK2 receptors, is needed to maintain the shape, size and activity of the ECL cells, but not for maintaining the ECL-cell population.

Animals↗
PubMed2000

Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice.

BACKGROUND & AIMS: Studies in gastrin-deficient mice have demonstrated critical roles for gastrin peptides in the regulation of gastric acid secretion, but the relative contributions of amidated (G-17) and glycine-extended (G17-Gly) gastrin remain unclear. We examined the effects of these 2 forms of gastrin on acid secretion in gastrin-deficient mice. METHODS: Sixty gastrin-deficient mice received infusions of saline, or 1, 6, or 14 days of amidated gastrin 17 (G-17), G17-Gly, or both G-17 and G17-Gly at 10 nmol. kg(-1). h(-1). Twenty-four gastrin-deficient mice were then infused for 14 days with 1, 2, or 5 nmol. kg(-1). h(-1) of G-17 or G-17 and G17-Gly. Acid secretion was determined 4 hours after pyloric ligation, and gastric tissue was processed for histology, immunohistochemistry, and electron microscopy. RESULTS: Infusion of G-17 increased acid secretion in a dose-dependent manner with a peak at 5 nmol. kg(-1). h(-1) and a subsequent decrease in acid secretion at higher doses. Infusion of G17-Gly alone had no effect on acid secretion, but coinfusion with G-17 resulted in significantly higher levels of acid secretion at all doses examined than infusion with G-17 alone. The potentiating effect of G17-Gly on G-17-induced acid secretion was associated with increased parietal cell activation but was independent of changes in parietal and enterochromaffin-like cell number, fundic proliferation rates, and H(+),K(+)-adenine triphosphatase expression. G17-Gly also prevented the formation of vacuolar canaliculi and lipofuscin bodies in the parietal cells induced by G-17. CONCLUSIONS: G17-Gly appears to synergize with G-17 to up-regulate acid secretion and prevent parietal cell degradation. These results suggest that G17-Gly plays an important role in parietal cell function.

Animals↗
PubMed1999

Effects of reserpine on ECL-cell ultrastructure and histamine compartmentalization in the rat stomach.

The histamine-storing ECL cells in the stomach play a key role in the control of acid secretion. They contain granules, secretory vesicles and microvesicles, and sustained gastrin stimulation results in the additional formation of vacuoles and lipofuscin bodies. The cells are rich in the vesicle monoamine transporter type-2 (VMAT-2), which can be inhibited by reserpine. The present study examines the effect of reserpine on ECL-cell ultrastructure and histamine compartmentalization. Rats received reserpine and/or gastrin. Reserpine was given twice by the intraperitoneal route (25 mg/kg once daily). Gastrin-17 was given by subcutaneous infusion (5 nmol/kg/h), starting at the time of the first reserpine injection and continuing for 4 days when the rats were killed. At this stage, histamine in the oxyntic mucosa was unaffected by reserpine but elevated by gastrin. Immunocytochemical analysis (confocal microscopy) showed ECL-cell histamine in control and gastrin-treated rats to be localized in cytoplasmic organelles (e.g., secretory vesicles). After treatment with reserpine alone or reserpine+gastrin, ECL-cell histamine occurred mainly in the cytosol. Planimetric analysis (electron microscopy) of ECL cells showed reserpine to increase the number, size and volume density of the granules and to reduce the size and volume density of the secretory vesicles. Gastrin reduced the number and volume density of granules and secretory vesicles, increased the number and volume density of microvesicles and caused vacuoles and lipofuscin bodies to appear. Reserpine+gastrin increased the number, volume density and size of the granules. Reserpine prevented the effects of gastrin on secretory vesicles, vacuoles and microvesicles, but did not prevent the development of lipofuscin. Our findings are in line with the views: (1) that preformed cytosolic histamine is taken up by granules/secretory vesicles via VMAT-2, that histamine is instrumental in the transformation of granules into secretory vesicles and in their consequent enlargement and (2) that vacuoles are formed by the fusion of large secretory vesicles.

Animals↗
PubMed1999

Secretory organelles in ECL cells of the rat stomach: an immunohistochemical and electron-microscopic study.

ECL cells are numerous in the rat stomach. They produce and store histamine and chromogranin-A (CGA)-derived peptides such as pancreastatin and respond to gastrin with secretion of these products. Numerous electron-lucent vesicles of varying size and a few small, dense-cored granules are found in the cytoplasm. Using confocal and electron microscopy, we examined these organelles and their metamorphosis as they underwent intracellular transport from the Golgi area to the cell periphery. ECL-cell histamine was found to occur in both cytosol and secretory vesicles. Histidine decarboxylase, the histamine-forming enzyme, was in the cytosol, while pancreastatin (and possibly other peptide products) was confined to the dense cores of granules and secretory vesicles. Dense-cored granules and small, clear microvesicles were more numerous in the Golgi area than in the docking zone, i.e. close to the plasma membrane. Secretory vesicles were numerous in both Golgi area and docking zone, where they were sometimes seen to be attached to the plasma membrane. Upon acute gastrin stimulation, histamine was mobilized and the compartment size (volume density) of secretory vesicles in the docking zone was decreased, while the compartment size of microvesicles was increased. Based on these findings, we propose the following life cycle of secretory organelles in ECL cells: small, electron-lucent microvesicles (pro-granules) bud off the trans Golgi network, carrying proteins and secretory peptide precursors (such as CGA and an anticipated prohormone). They are transformed into dense-cored granules (approximate profile diameter 100 nm) while still in the trans Golgi area. Pro-granules and granules accumulate histamine, which leads to their metamorphosis into dense-cored secretory vesicles. In the Golgi area the secretory vesicles have an approximate profile diameter of 150 nm. By the time they reach their destination in the docking zone, their profile diameter is between 200 and 500 nm. Exocytosis is coupled with endocytosis (membrane retrieval), and microvesicles in the docking zone are likely to represent membrane retrieval vesicles (endocytotic vesicles).

Animals↗
PubMed1999

Rat stomach ECL cells up-date of biology and physiology.

The ECL cell is the predominant endocrine cell type in the oxyntic mucosa, displaying typical ultrastructure with numerous cytoplasmic vesicles and electron-dense granules. ECL cells have many features in common with neurons and other peptide hormone-producing endocrine cells, including the ability to produce, store, and secrete chromogranin-A and chromogranin A-derived peptides. In addition, they produce and store histamine and respond with activation and growth to a gastrin challenge. ECL cells are stimulated to secrete histamine as well as other products by gastrin and PACAP and are inhibited by somatostatin, galanin, and prostaglandins. The cytoplasmic vesicles are thought to contain histamine and other secretory products. Mature secretory vesicles occur in the docking zone of the ECL cells, where they constitute the releasable pool of secretory products. Gastrin stimulation will induce exocytosis and degranulation. Histamine released from ECL cells plays a key role in the regulation of parietal cell activity (the gastrin-ECL cell-parietal cell axis). In response to long-term gastrin stimulation, vacuoles and lipofuscin bodies develop in the ECL cells, forming part of a crinophagic pathway by which the ECL cell strives to eliminate superfluous secretory products.

Animals↗
PubMed1999

Expression of a novel chimeric protein containing the A chain of tissue-type plasminogen activator and the B chain of pro-urokinase in insect cells using the baculovirus system.

A hybrid cDNA tu-pa, which contains Ser1-Thr263 of tissue-type plasminogen activator (t-PA) and Ser138-Leu411 of pro-urokinase (pro-UK) was constructed and expressed in the Sf9-AcNPV system. The expression level was approximate 2.5 mg/L. Tu-PA was purified via one-step affinity column conjugated with monoclonal antibody against the B chain of pro-UK, which showed a single band of approximate 60 kDa in SDS-PAGE. The specific activity of the chimeric protein on fibrin plate was 200,000 IU/mg protein. Tu-PA had a higher selectivity for fibrin than UK and pro-UK. Its activity can be promoted by CNBr degraded fibrin fragments as t-PA.

Animals↗
PubMed1998

Novel aspects of gastrin-induced activation of histidine decarboxylase in rat stomach ECL cells.

The ECL cells in the rat stomach respond to gastrin with secretion of histamine and activation of the histamine-forming enzyme histidine decarboxylase (HDC). In the present study, we have investigated factors that influence gastrin-induced activation of HDC. Gastrin-17 was given by continuous intravenous infusion to fasted and freely fed rats in various doses and for various periods of time. We found that: (1) ECL cells in fasted rats displayed one order of magnitude higher sensitivity to gastrin (3 h infusion) than did ECL cells in fed rats (ED50 0.4 versus 4.0 nmol kg(-1) h(-1)), while the maximum response to gastrin was two times greater in fed rats than in fasted rats; (2) HDC in both fasted and fed rats responded to a high gastrin dose (5 nmol kg(-1) h(-1)) in a biphasic manner with peak activity after 8 h in fasted rats and after 16 h in fed rats. In both groups, the activation was followed by a marked decline in the enzyme activity to almost prestimulation levels 24 h after start of the infusion. A low gastrin dose (0.4 nmol kg(-1) h(-1)) did not induce such a biphasic response. Maximum activation of HDC in fed rats occurred 6 days after starting the infusion of the low gastrin dose and was two times higher than the maximum activation observed after the high gastrin dose; (3) In fasted rats the HDC mRNA level rose in response to the high gastrin dose, peaked after 8 h (twofold increase) and then returned to the prestimulation level. In fed rats the increase was slower, reaching a plateau after 24 h that lasted for 6 days (twofold increase); (4) The translation inhibitor cycloheximide blocked the activation of HDC induced by gastrin (4 h infusion of 5 nmol kg(-1) h(-1)), while the transcription inhibitor actinomycin D, which suppressed the increase in HDC mRNA expression, did not.

Animals↗
PubMed1998

ECL cells of the rat stomach: development of lipofuscin in response to sustained gastrin stimulation.

Ageing cells, especially post-mitotic cells, are known to accumulate pigments, i.e. highly electron-dense material, referred to as ceroid or lipofuscin. This material is formed as a consequence of autophagocytosis and peroxidation of the products undergoing degradation. The present study describes the development of lipofuscin in the ECL cells of the rat stomach. These cells produce and secrete histamine in response to gastrin. They are rich in secretory vesicles, which fuse to form vacuoles in hypergastrinaemic rats. Hypergastrinaemia was induced by continuous infusion of human Leu15-gastrin-17 for 6 days or by daily treatment with omeprazole for 10 weeks. Either treatment caused both vacuoles and lipofuscin bodies to appear in large numbers; the vacuoles disappeared promptly after interruption of the hypergastrinaemia, whereas the lipofuscin bodies remained. Antrectomy-evoked hypogastrinaemia was associated with a reduced number and volume density of lipofuscin bodies. Treatment with alpha-fluoromethylhistidine, an irreversible inhibitor of the histamine-forming enzyme, resulted in depletion of ECL-cell histamine and was found to prevent the omeprazole-evoked formation of vacuoles and lipofuscin. The numbers of both vacuoles and lipofuscin bodies were well-correlated with the serum gastrin concentration, suggesting that gastrin stimulates the development not only of vacuoles but also of lipofuscin, perhaps through enhanced autophagocytosis and/or oxidative stress. Thus, lipofuscin bodies may develop from vacuoles, and both vacuoles and lipofuscin bodies may reflect the efforts of overstimulated ECL cells to cope with the excessive formation of secretory products.

Animals↗
PubMed1997

Functional impairment of the individual rat stomach ECL cell in response to sustained hypergastrinemia.

ECL cells in the oxyntic mucosa secrete histamine and pancreastatin in response to gastrin. The present study examined gastrin-evoked ECL-cell responses over a 10-week time span in terms of individual ECL cells and unit ECL cell volume. Rats were treated with omeprazole (400 micromol/kg per day orally). The concentrations of gastrin and pancreastatin in serum and of histamine and pancreastatin in the oxyntic mucosa were measured as was the activity of the oxyntic mucosal histidine decarboxylase (HDC). The ECL cells were visualized by immunostaining of histamine and examined by electron microscopy. The total ECL cell number and volume, and the mean ECL cell diameter and volume were determined. The HDC, chromogranin A (CGA) and cholecystokinin-B (CCK-B) receptor mRNA concentrations were determined. In terms of individual ECL cells and unit ECL cell volume, the serum pancreastatin concentration, the oxyntic mucosal histamine content, HDC activity, and HDC, CGA and CCK-B receptor mRNA contents increased slowly at first and then leveled off or started to decline after 2 weeks. After 10 weeks all ECL-cell parameters (expressed per unit ECL cell volume) were back to or approaching the starting value. In conclusion, sustained hypergastrinemia first activates each individual ECL cell (with a peak after 1-2 weeks) and then causes gradual functional impairment, the activity returning towards the pre-stimulation level.

Animals↗
PubMed1997

Neurohormonal regulation of histamine and pancreastatin secretion from isolated rat stomach ECL cells.

ECL cells are numerous in the acid-producing part of the rat stomach. They are rich in histamine and pancreastatin, a chromogranin A-derived peptide, and they secrete these products in response to gastrin. We have examined how isolated ECL cells respond to a variety of neuromessengers and peptide hormones. Highly purified (85%) ECL cells were collected from rat stomach using repeated counter-flow elutriation and cultured for 48 h before experiments were conducted. The ECL cells responded to gastrin, sulphated cholecystokinin-8 and to high K+ and Ca2+ with the parallel secretion of histamine and pancreastatin. Glycine-extended gastrin was without effect. Forskolin, an activator of adenylate cyclase, induced secretion, whereas isobutylmethylxanthine, a phosphodiesterase inhibitor, raised the basal release without enhancing the gastrin-evoked stimulation. Maximum stimulation with gastrin resulted in the release of 30% of the secretory products. Numerous neuromessengers and peptide hormones were screened for their ability to stimulate secretion and to inhibit gastrin-stimulated secretion. Pituitary adenylate cyclase activating peptide (PACAP)-27 and -38 stimulated secretion of both histamine and pancreastatin with a potency greater than that of gastrin and with the same efficacy. Related peptides, such as vasoactive intestinal peptide, helodermin and helospectin, stimulated secretion with lower potency. The combination of EC100 gastrin and EC50 PACAP produced a greater response than gastrin alone. None of the other neuropeptides or peptide hormones tested stimulated secretion. Serotonin, adrenaline, noradrenaline and isoprenaline induced moderate secretion at high concentrations. Muscarinic receptor agonists did not stimulate secretion, and histamine and selective histamine receptor agonists and antagonists were without effect. This was the case also with GABA, aspartate and glutamate. Somatostatin and galanin, but none of the other agents tested, inhibited gastrin-stimulated secretion. Our results reveal that not only gastrin but also PACAP is a powerful excitant of the ECL cells, that not only somatostatin, but also galanin can suppress secretion, that muscarinic receptor agonists fail to evoke secretion, and that histamine (and pancreastatin) does not evoke autofeedback inhibition.

Animals↗
PubMed1997

Expression of the chromogranin A-derived peptides pancreastatin and WE14 in rat stomach ECL cells.

The ECL cells constitute the predominant endocrine cell population in the mucosa of the acid-secreting part of the stomach (fundus). They are rich in chromogranin A (CGA), histamine and histidine decarboxylase (HDC). They secrete CGA-derived peptides and histamine in response to gastrin. The objective of this investigation was to examine the expression of pancreastatin (rat CGA266-314) and WE14 (rat CGA343-356) in rat stomach ECL cells. The distribution and cellular localisation of pancreastatin- and WE14-like immunoreactivities (LI) were analysed by radioimmunoassay and immunohistochemistry with antibodies against pancreastatin, WE14 and HDC. The effect of food deprivation on circulating pancreastatin-LI was examined in intact rats and after gastrectomy or fundectomy. Rats received gastrin-17 (5 nmol/kg/h) by continuous intravenous infusion or omeprazole (400 micromol/kg) once daily by the oral route, to induce hypergastrinemia. CGA-derived peptides in the ECL cells were characterised by gel permeation chromatography. The expression of CGA mRNA was examined by Northern blot analysis. Among all of the endocrine cells in the body, the ECL cell population was the richest in pancreastatin-LI, containing 20-25% of the total body content. Food deprivation and/or surgical removal of the ECL cells lowered the level of pancreastatin-LI in serum by about 80%. Activation of the ECL cells by gastrin infusion or omeprazole treatment raised the serum level of pancreastatin-LI, lowered the concentrations of pancreastatin- and WE14-LI in the ECL cells and increased the CGA mRNA concentration. Chromatographic analysis of the various CGA immunoreactive components in the ECL cells of normal and hypergastrinemic rats suggested that these cells respond to gastrin with a preferential release of the low-molecular-mass forms.

Animals↗
PubMed1997

Evidence that rat stomach ECL cells represent the main source of circulating pancreastatin.

Recently, we showed that the ECL cells in the oxyntic mucosa of the rat stomach are an important source of circulating pancreastatin, a fragment of chromogranin A. The present study examined how much the ECL cells contribute to the circulating levels of pancreastatin during omeprazole-evoked hypergastrinemia. Rats received omeprazole (400 mumol kg-1 day-1) by the oral route for 3 weeks. Two weeks after the start of the treatment, the rats were subjected to a sham operation or fundectomy. The concentrations of gastrin and pancreastatin in serum were monitored before and after the operations. The ECL cells were visualized by pancreastatin immunostaining and their number was determined. The activity of oxyntic mucosal histidine decarboxylase (HDC) was measured before and after 2 weeks of omeprazole treatment. Omeprazole-induced hypergastrinemia resulted in elevated serum pancreastatin and increased oxyntic mucosal HDC activity. Pancreastatin-immunoreactive cells were equally numerous before and after 2 weeks of omeprazole treatment. After surgical removal of the ECL cells by fundectomy, the serum gastrin concentration remained high whereas the serum pancreastatin concentration decreased by 90%. We conclude that the ECL cells in omeprazole-treated rats are responsible for 90% of circulating pancreastatin.

Animals↗
PubMed1997

Exocytotic proteins in enterochromaffin-like (ECL) cells of the rat stomach.

Proteins participating in vesicular docking and fusion have been identified in the nervous system. Such proteins appear to be important for the molecular regulation of exocytosis also in non-neuronal cells. The enterochromaffin-like (ECL) cells of the gastric acid-secreting (oxyntic) mucosa secrete histamine and chromogranin A-derived peptides, such as pancreastatin. Using immunohistochemistry, we have examined whether the ECL cells of the rat stomach, identified with antibodies to histidine decarboxylase (HDC, the histamine-forming enzyme), express the same exocytotic proteins as neurons. The ECL cells displayed immunoreactivity for synaptophysin, synaptotagmin III, vesicle-associated membrane protein-2 (VAMP-2), cysteine string protein (CSP), vesicular monoamine transporter-2 (VMAT-2), synaptosomal-associated protein of 25 kDa (SNAP-25), syntaxin, and Munc-18, but not for synaptotagmin I/II and VAMP-1. Synaptophysin and VMAT-2 could be detected not only in the ECL cells, but also in a population of HDC-negative cells. The demonstration of synaptotagmin III in only a limited number of ECL cells suggests the existence of a subpopulation of ECL cells. The results show that several exocytotic proteins, previously identified in neurons, are present in rat stomach ECL cells. Hence, proteins engaged in vesicular docking and in the fusion of granule/vesicle membrane with plasma membrane seem to exist in both neurons and endocrine cells.

Animals↗