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PubMed1987

Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms.

Using a recently developed canine primary enteric endocrine cell culture system, we have investigated the role of adenosine 3',5'-cyclic monophosphate (cAMP) in mediating the release of neurotensin and enteroglucagon. Epinephrine-stimulated peptide release was concomitant with an increase in cAMP accumulation. Carbachol and somatostatin (SRIF) markedly inhibited the epinephrine effect on both peptide release and cAMP content. The addition of 3-isobutyl-1-methylxanthine potentiated epinephrine-stimulated peptide release without altering the relative inhibition by carbachol and SRIF, suggesting that these agents did not inhibit endocrine cell function by increasing phosphodiesterase activity. To determine the role of cAMP production in mediating inhibition of peptide release, cells were incubated with the bacterial toxin, pertussis toxin (PT). In cultures pretreated with PT, carbachol inhibition of both peptide release and cAMP accumulation was completely reversed. In contrast, SRIF inhibition of cAMP content was completely reversed after PT treatment, but inhibition of peptide release was only partially reversed. Additionally, toxin treatment only partially reversed SRIF inhibition of forskolin- and calcium ionophore-stimulated peptide release. These data suggest that muscarinic cholinergic inhibition of neurotensin and enteroglucagon release is mediated entirely through the guanine nucleotide-binding protein (Ni) or a similar toxin-sensitive, GTP-binding protein. SRIF-inhibited peptide release is mediated partially through a toxin-sensitive substrate, as evidenced by PT reversal of reduced cAMP levels. SRIF may also inhibit neurotensin and enteroglucagon release by a cAMP-independent pathway that is not coupled to Ni or a similar PT-sensitive, GTP-binding protein.

1-Methyl-3-isobutylxanthine↗
PubMed2004

Ghrelin stimulates gastric emptying but is without effect on acid secretion and gastric endocrine cells.

Ghrelin, a recently discovered peptide hormone, is produced by endocrine cells in the stomach, the so-called A-like cells. Ghrelin binds to the growth hormone (GH) secretagogue receptor and releases GH. It is claimed to be orexigenic and to control gastric acid secretion and gastric motility. In this study, we examined the effects of ghrelin, des-Gln14-ghrelin, des-octanoyl ghrelin, ghrelin-18, -10 and -5 (and motilin) on gastric emptying in mice and on gastric acid secretion in chronic fistula rats and pylorus-ligated rats. We also examined whether ghrelin affected the activity of the predominant gastric endocrine cell populations, G cells, ECL cells and D cells. Ghrelin and des-Gln14-ghrelin stimulated gastric emptying in a dose-dependent manner while des-octanoyl ghrelin and motilin were without effect. The C-terminally truncated ghrelin fragments were effective but much less potent than ghrelin itself. Ghrelin, des-Gln14-ghrelin and des-octanoyl ghrelin neither stimulated nor inhibited gastric acid secretion, and ghrelin, finally, did not affect secretion from either G cells, ECL cells or D cells.

Animals↗
PubMed1981

Fine structure of the gastric mucous and endocrine cells of the toad, Bufo marinus.

The ultrastructure of the mucous and endocrine cells of the gastric mucosa of the cane toad (Bufo marinus) has been examined. Surface mucous cells line the entire gastric mucosa and pits. Many of their secretory granules contain an electro-dense core that remains unreactive after cytochemical testing for glycoproteins. A second spatially and structurally discrete population of mucous cells is present in the gastric glands. These glandular mucous cells are probably homologous with the antral gland and mucous neck cells of mammals; their secretory granules also contain non-glycoprotein cores. Three distinct populations of endocrine cells show structural homologies with gastric hormone-storing cells of higher vertebrates.

Animals↗
PubMed1979

Spontaneous argyrophil cell carcinoid in the glandular stomach: immunohistochemical study of gastric endocrine cells in normal and tumour-bearing mastomys.

Endocrine tumours (argyrophil cell carcinoids) are frequent in the oxyntic mucosa of mastomys. The tumour is notable for its high histamine content and for its high histidine decarboxylase activity. The tumour is thought to arise from the histamine-storing, enterochromaffin-like cells of the oxyntic mucosa. They are of two ultrastructurally distinguishable types, ECL cells and A-like cells, both of which have been demonstrated in the tumour. Identical cells have been demonstrated in the oxyntic mucosa of the rat; there is much evidence that in this species the functional activity and the number of these cells are determined by the serum gastrin concentration. However, tumours have never been found to arise from these cells in the rat. As an initial step in an attempt to explain the formation of the gastric endocrine tumour in the mastomys we examined the distribution and frequency of occurrence of endocrine cells in the mastomys stomach. Gastrin cells in the antrum of mastomys seemed to occur in about the same frequency as in the antrum of rat and mouse. 5-HT-storing enterochromaffin cells, however, were considerably more numerous in the mastomys, whereas the somatostatin cells in the antrum were fewer. The number of enterochromaffin-like cells and somatostratin cells in the oxyntic mucosa of mastomys was much lower than in the rat and mouse. Once developed, the gastric endocrine tumour seems to reduce the antral gastrin cell number; the larger the tumour the greater the reduction.

Animals↗
PubMed1987

Gastric carcinoid tumors, endocrine cell hyperplasia, and associated intestinal metaplasia. Histologic, histochemical, and immunohistochemical findings.

Eleven cases of gastric carcinoid tumor have been studied to review their clinical and pathologic spectrum, to identify any relationship to pernicious anemia, and to evaluate the accompanying gastric mucosal changes, with particular reference to the endocrine cell population. Seven patients were male and four female; ages ranged from 26 to 83 years. Two male patients had documented pernicious anemia and one female patient had unconfirmed pernicious anemia. All patients had marked gastric intestinal metaplasia (atrophic gastritis), which was predominantly fundal (Type A) in three patients with suspected/proven pernicious anemia and antral (Type B) in the other eight. In seven patients, the tumors were typical carcinoids, whereas in 4 patients the carcinoids were "atypical"; one carcinoid was completely polypoid. All cases were argyrophilic, and focal mucin positivity was present in four. Focal somatostatin immunoreactivity was present in four cases, serotonin in three cases, vasoactive intestinal polypeptide (VIP) in two cases, and gastrin (G) in one case. Endocrine cell hyperplasia was identified in the gastric mucosa of eight of 11 patients, including all cases with pernicious anemia; in three of eight cases, G-cell hyperplasia was evident. Numbers of serotonin-positive cells were increased in areas of intestinal metaplasia in all cases. In two patients, there was marked endocrine-cell hyperplasia with multiple small carcinoid tumorlets; the tumorlets stained for G in one. Gastric intestinal metaplasia includes intestinal-like endocrine cells. An association exists between atrophic gastritis and gastric carcinoids, and there is a histogenetic link between atrophic gastritis and some cases of gastric carcinoid tumor.

Adult↗
PubMed1993

Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance.

The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.

Adenocarcinoma↗
PubMed1988

Immunohistochemical localization of some endocrine cells in the gastroenteropancreatic system of Erinaceus europaeus.

The distribution of chromogranin A and neuron specific enolase (NSE) in the neuroendocrine gut system and the morphology and distribution of cells containing gastrin, somatostatin, neurotensin and VIP in the gastroenteropacreatic (GEP) apparatus of Erinaceus europaeus were investigated by immunohistochemical methods. Chromogranin A and somatostatin immunoreactive cells were present throughout the gastrointestinal mucosa, with the exception of the oesophagus and in the pancreas. Gastrin cells were peculiar of the pyloric glands and duodenal mucosa and neurotensin cells of the small intestine. No VIP immunoreactive endocrine cells were noticed in the GEP system. VIP and NSE immunoreactivities were detected both in nerve cell bodies and terminals of the wall of the GEP apparatus. NSE immunoreactivity was found in the endocrine cells of the fundic and pyloric mucosa.

Animals↗
PubMed2004

An immunohistochemical study of the gastrointestinal endocrine cells in the ddY mice.

The distributions and frequencies of some endocrine cells in the gastrointestinal (GI) tract of ddY mice were studied with immunohistochemical method using 7 types of antisera against bovine chromogranin (BCG), serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin, glucagon and human pancreatic polypeptide (HPP). All of 7 types of immunoreactive (IR) cells were identified. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open typed cell) while cells showing round in shape (close typed cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of GI tract. BCG-IR cells were demonstrated throughout whole GI tract except for the cecum and they were most predominant in the fundus and pylorus. Serotonin-IR cells were detected throughout whole GI tract and they were most predominant cell types in this species of mice. Gastrin-IR cells were restricted to the pylorus and CCK-8-IR cells were demonstrated in the pylorus, duodenum and jejunum with numerous frequencies in the pylorus. Somatostatin-IR cells were detected throughout whole GI tract except for the cecum and rectum and they showed more numerous frequencies in the stomach regions. In addition, glucagon-IR cells were restricted to the fundus, duodenum and jejunum with rare frequencies, and HPP-IR cells were restricted to the rectum only with rare frequency. In conclusion, some strain-dependent unique distributional patterns of gastrointestinal endocrine cells were found in GI tract of ddY mice.

Animals↗
PubMed1994

[3H]GABA uptake and GABA localization in mucosal endocrine cells of the rat stomach and colon.

The aim of this study was to characterize the distribution of GABAergic cells in the rat gut mucosa. Thin and/or thick serial sections of segments of rat antrum and distal colon were treated for autoradiographic localization of sites of [3H]GABA (50 nM) high-affinity uptake, or GABA immunoreactivity. Dense accumulations of silver grains were localized to a discrete population of granulated mucosal cells. These appeared to be D-type endocrine cells. These gut regions also displayed strongly GABA-immunoreactive mucosal cells. These results confirm the presence of GABAergic cells in the rat antral mucosa, and reveal that [3H]GABA is accumulated by mucosal endocrine cells in the rat colon.

Animals↗
PubMed1982

Rectal carcinoids as tumors of the hindgut endocrine cells: a morphological and immunohistochemical analysis.

The rectal mucosa is richly endowed with a constellation of amine and polypeptide hormone-producing endocrine cell types which may be identified by silver staining and immunohistochemical methods. In order to study the relationships of rectal carcinoid tumors to the normal hindgut endocrine cells, rectal carcinoids and normal rectal mucosa were compared for the presence of argentaffinity and argyrophilia and for the distribution of a battery of polypeptide hormones. Normal rectal mucosa contained frequent cells which stained for bovine pancreatic polypeptide (PP), human PP, and glucagon-like immunoreactivity (GLI. Somatostatin (SRIF) was present in a smaller proportion of rectal endocrine cells. Both argentaffin and argyrophil cells were encountered frequently in normal rectal mucosa. In the series of 13 rectal carcinoids examined, two cases were focally argentaffin-positive, while eight tumors revealed varying degrees of argyrophilia. Eight tumors contained immunoreactive bovine PP, and four of these tumors which were tested for human PP were also positively stained. SRIF was present in five cases, while GLI was identified in two tumors. Four of the tumors were multihormonal. Rectal carcinoids have a rich polypeptide hormone content which parallels that of the normal rectal mucosa. The distinctive hormonal profile and silver staining properties may prove to be of value as specific markers for carcinoid tumors of rectal or hindgut origin.

Animals↗
PubMedDate not supplied

Circadian rhythm in the mitotic activity of the pars intermedia endocrine cell population of the mouse.

A mitotic circadian rhythm is reported for the endocrine cells of the pars intermedia of mouse pituitary. The peak is observed at 0000 and the trough at 1600. This curve is about 12h out of phase with the curves of mitotic activity of most of the cell populations of the organism of the mouse which show peaks about noon (1200). A similar inverted mitotic rhythm has been reported for corticoadrenal since a long time ago. The results are discussed in relation with the contradiction existing between proliferation and function in cell populations. The conclusion is drawn that the endocrine cells of the pars intermedia could represent another link in the circadian system controlling periodicity.

Animals↗
PubMed1988

Pulmonary adenoma and endocrine cell hyperplasia in Syrian golden hamster treated with 4-nitroquinoline 1-oxide.

Chronic effects of 4-nitroquinoline 1-oxide (4 NQO) on the lungs of Syrian golden hamsters were studied. 4 NQO was subcutaneously injected weekly for 3 weeks at a dose of 20 mg/kg body weight. The animals were sacrificed at the 65th and 80th experimental weeks. Two cases of pulmonary adenomas were demonstrated in the 10 4 NQO-treated animals at the 80th week, and the tumor cells contained cytoplasmic lamellar inclusion bodies. In a previous study, we reported 4 NQO- induced pulmonary endocrine cell hyperplasias in the 4 NQO-treated hamster after the 20th experimental week (Jpn. J. Cancer Res., 77, 1986). In the present study, 12 pulmonary endocrine cell hyperplasias were recognized in serial sections of the 24 treated animals. The hyperplastic lesions showed positive immunoreactivity to calcitonin. The hyperplastic lesion did not develop to pulmonary endocrine cell neoplasm.

4-Nitroquinoline-1-oxide↗
PubMed2001

Preliminary immunohistochemical study of C cells of the thyroid and endocrine cells of the parathyroid glands in rats after prolonged exposure to cadmium.

The effect of cadmium (Cd) on the thyroid and parathyroid glands was examined following a 12-week exposure of rats to 5 or 50 mg Cd/dm3. Immunohistochemical methods were used to determine calcitonin (CT), calcitonin-gene related peptide (GGRP), parathormone (PTH), somatostatin (ST), synaptophysin (SPh) and neuron-specific enolase (NSE). Calcium and cadmium concentrations in the femoral bone were assayed. The animals exposed to cadmium showed attenuation of all reactions, which was most distinct after 50 mg Cd/dm3. Exposure-dependent cadmium accumulation and a decrease in calcium concentration in the femoral bone were noted.

Animals↗
PubMed1981

Regulatory peptides in endocrine cells and autonomic nerves: electron immunocytochemistry.

Advances in immunocytochemistry, particularly at the electron microscope level, have enabled us to establish further details of the ultrastructural appearance of endocrine cells and autonomic nerves of the gastrointestinal tract. Its contribution can be summarised as follows: a)validation of previously recognised endocrine cell types. b) Recognition of sub-groups within endocrine cells and autonomic nerve cell types previously included within one single type (e.g. D1 cells and p-type autonomic nerves). c) Discrimination of molecular forms now known to be stored in morphologically distinguishable secretory granules or parts thereof (e.g. pro-glucagon and glucagon in A cells and gut and antral gastrin-producing cells). Advances in the techniques and the accurate quantification of the end products will enable us to recognise changes in gastrointestinal tract diseases in man.

Animals↗
PubMed1986

Immunohistochemical morphometry of pancreatic endocrine cells in diabetic, normoglycaemic glucose-intolerant and normal cats.

The anatomical distribution and volume fractions of pancreatic A cells (glucagon), B cells (insulin) and D cells (somatostatin) were evaluated by an immunoperoxidase technique in 6 diabetic cats, 6 normoglycaemic glucose-intolerant cats and 6 normal control cats. Islets lacking A cells were observed in some sections from the right lobe of the pancreas which correlated with a significantly lower A cell volume fraction in the right pancreatic lobe. Endocrine cell volume fractions in normoglycaemic glucose-intolerant cats were not significantly different from controls. Thus, a reduction in B cell volume fraction was not necessary for the occurrence of impaired glucose tolerance in these cats. However, the reduction of B cell volume fraction in the 2 normoglycaemic glucose-intolerant cats with insular amyloidosis may in part explain the more severely impaired glucose tolerance previously observed in these cats. Insular amyloidosis in our feline diabetics, as in human type II diabetics, was associated with a significant decrease in A and B cell volume fractions. In both human type II and feline diabetes mellitus, however, the reduction in B cell mass does not appear sufficient alone to lead to diabetes mellitus. Therefore, amyloid replacement of functional endocrine cells does not appear to be the primary diabetogenic event in feline diabetes mellitus, but may contribute to progression of the condition due to loss of functional B cell reserves. We thus postulate that a B cell defect precedes deposition of islet amyloid and that these amyloid deposits may thus provide an important biochemical clue to specific B cell derangements occurring in adult-onset diabetics.

Amyloidosis↗
PubMed1981

Demonstration of carboxyl-terminal PP-like peptides in endocrine cells and nerves.

Pancreatic polypeptide (PP) has been isolated from the pancreas of several species, and has been localized by immunohistochemistry to a distinct population of pancreatic endocrine cells. Recently, PP-like immunoreactivity has been demonstrated outside the pancreas, in gut endocrine cells and central and peripheral nerves, in studies using antisera raised to natural PPs. The antigenic determinants recognised by these antisera are not known in any detail, and, therefore, the identity of the molecules in these extrapancreatic localizations is also unknown. We have raised an antiserum to the synthetic COOH-terminus of PP (PP6), which, therefore, is directed exclusively towards the biologically active, invariant region of mammalian PPs. PP6-like immunoreactivity was localized in pancreatic cells which were revealed also by antiserum to human PP (hPP). Outside the pancreas, no localizations were obtained with anti-hPP antiserum, whereas antiserum to PP6 demonstrated immunoreactivity in a variety of tissues including gut glucagon cells, adrenal chromaffin cells, and nerve fibres in the gastrointestinal tract and adrenal gland. We would suggest that the wide distribution in nerves and endocrine cells of PP6-immunoreactive material, which may be biologically active, should be taken into account in the search for a physiological role for PP.

Adrenal Glands↗
PubMed1994

Activity-dependent mobilization of the adhesion molecule polysialic NCAM to the cell surface of neurons and endocrine cells.

The alpha-2,8-linked sialic acid polymer (PSA) on the neural cell adhesion molecule (NCAM) is an important regulator of cell surface interactions. We have examined the translocation of PSA-NCAM to the surface of cultured cortical neurons and insulin secreting beta cells under different conditions of cell activity. Endoneuraminidase N, an enzyme that specifically cleaves PSA chains, was used to remove pre-existing PSA from the plasma membrane and the re-expression of the molecule was monitored by immunocytochemistry. Punctate PSA immunostaining was restored on the surface of 68% of neurons within 1 h. This recovery was almost completely prevented by tetrodotoxin, suggesting that spontaneous electrical activity is required. K+ depolarization (50 mM) allowed recovery of PSA surface staining in the presence of tetrodotoxin and this effect required the presence of extracellular Ca2+. Rapid redistribution of PSA-NCAM to the surface of beta cells was observed under conditions that stimulate insulin secretion. Ca2+ channel inhibition decreased both PSA-NCAM expression and insulin secretion to control, non-stimulated levels. Finally, subcellular fractionation of an insulin-secreting cell line showed that the secretory vesicle fraction is highly enriched in PSA-NCAM. These results suggest that PSA-NCAM can be translocated to the cell surface via regulated exocytosis. Taken together, our results provide unprecedented evidence linking cell activity and PSA-NCAM expression, and suggest a mechanism for rapid modulation of cell surface interactions.

Animals↗
PubMed2001

Single K+ channels in endocrine cells dispersed from the cricket (Gryllus bimaculatus) corpora allata.

Single channel currents were recorded from cell-attached patches of endocrine cells of the adult male cricket corpora allata. Three distinct types of K+ channels were identified; a weak inward rectifier (Type 1), a strong inward rectifier (Type 2) and a weak outward rectifier (Type 3). The type 1 channel had a slope conductance of 191 +/- 9 pS (n = 4) at negative membrane potentials (Vm) and 101 +/- 6 pS (n = 6) at positive Vm. In addition, the channel showed fast open-closed kinetics at negative Vm and slow open-closed kinetics at positive Vm. The open probability (Po) of this channel was strongly voltage-dependent at positive Vm, but less voltage-dependent at negative Vm. The reversal potential was not modified significantly by the substitution of gluconate for external Cl- but was modified after N-methyl-D-glucamine (NMDG+) was substituted for external K+, according to the Nernst equation for a K+-selective channel. The type 2 channel had a slope conductance of 44 +/- 2 pS (n = 5) at negative Vm, but no detectable outward current was observed at positive Vm. This channel showed very slow open-closed kinetics at negative Vm and its Po was not voltage-dependent. The type 3 channel had a limit conductance of 55 +/- 12 pS (n = 3) at negative Vm and 88 +/- 10 pS (n = 3) at positive Vm. This channel showed slow open-closed kinetics at negative Vm and fast open-closed kinetics at positive Vm. The Po for the channel was voltage-dependent at positive Vm but was voltage-independent at negative Vm. These three types of K+ channels may be important for the control of the resting membrane potential, and may thus participate in the regulation of Ca2+ influx and juvenile hormone secretion in corpora allata cells.

Animals↗