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PubMed1989

Chromogranin A (CgA) in the gastro-entero-pancreatic (GEP) endocrine system. II. CgA in mammalian entero-endocrine cells.

Chromogranin A (CgA) and related acidic proteins are widely distributed in the organism. They are also present in entero-endocrine cells and in other members of the paraneuron family. Therefore, CgA has been claimed as an universal marker of this cellular community. To yield precise data about the distribution of CgA in entero-endocrine cells, all segments of the gastro-intestinal tract of five mammalian species (man, cattle, pig, cat, guinea-pig) were investigated immunohistochemically for CgA. In serial semithin plastic sections, all CgA-immunoreactive endocrine cells were identified for resident amines or peptides. CgA could be found in ten hormonally identified endocrine cell types and in two or three other endocrine cell types. Entero-endocrine cells containing amines (histamine, serotonin) regularly exhibited CgA-immunoreactivities. In contrast, peptide-containing endocrine cells were largely heterogeneous: Their CgA-immunoreactivities varies among the species, among the gastro-intestinal segments, and even among the members of the same cell population. Hence, seen histochemically, CgA is no universal marker for entero-endocrine cells. Seen biochemically, the observed heterogeneities of CgA-immunoreactivities theoretically can be attributed to various factors (species-specificities of CgA, subclasses of chromogranins, processing of CgA or its pro-protein). Most probably, these heterogeneities are caused by species- or cell-specific differences in the extent of processing of CgA. In addition, some findings point to certain interrelations between the processing or storage of CgA and resident peptides in the secretion granules of enteroendocrine cells.

Animals↗
PubMed1996

Nucleotide vesicular transporter of bovine chromaffin granules. Evidence for a mnemonic regulation.

The nucleotide vesicular transport has been studied with the fluorescent substrate analogues, the (1,N6-ethenoadenosine) nucleotides. The transport experiments were carried out with granular preparations from bovine adrenal medulla, and epsilon-ATP, epsilon-ADP, and epsilon-AMP were quantified after separation by high performance liquid chromatography. The granular concentration increase of all three nucleotides was time-dependent. The concentration dependence of epsilon-nucleotide transport to chromaffin granules did not follow the Michaelis-Menten kinetics and presented a similar three-step curve with cooperativity. This shape can be considered to be the result of the addition of three sigmoidal curves with their corresponding kinetic parameters. epsilon-ATP exhibited K values of 0.25, 1, and 3 mM and Vmax values of 0.02, 0.04 and 0.19 nmol.min-1.mg of protein-1, for the first, second, and third curves for each step, respectively. epsilon-ADP exhibited K values of 0.15, 0.9, and 3.6 mM and Vmax values of 0.025, 0.035, and 0.3 nmol.min-1.mg of protein-1, respectively for the first, second, and third curves. epsilon-AMP exhibited K values of 0.2, 1.2, and 3.2 mM, and Vmax values of 0.01, 0.04, and 0.055 nmol.min-1.mg of protein-1, also for the first to third steps. The Hill numbers for epsilon-ATP, epsilon-ADP, and epsilon-AMP were not constant but a function of the transport saturation. The nonhydrolyzable ATP analogues AMPPNP, ATP gamma S, and ADP beta S were activators of epsilon-nucleotide transport at concentrations under 1 mM and inhibitors at higher concentrations. Atractyloside and N-ethylmaleimide partially inhibited the nucleotide granular transport. High extragranular ATP concentrations specifically induced the exit of the previously transporter granular epsilon-ATP.

Adenine Nucleotides↗
PubMed1986

Identification and characterization of enterochromaffin cells with different staining techniques.

The staining characteristics of the enterochromaffin cell system in the human and rat gastrointestinal tract were studied with 3 histochemical procedures--the Masson method, formaldehyde-induced fluorescence (FIF), and immunocytochemical techniques using both monoclonal and polyclonal serotonin antisera. A simple modification of the Masson technique is described and compared with several other modifications of the same technique. The specificities of the 2 antisera were examined with regard to serotonin and other monoamines and their albumin conjugates, monoamine precursors and metabolites, and also to serotonin-related substances. In the intestine, with very few exceptions the same cells reacted positively with the 3 staining methods, but often serotonin immunoreactivity was observed in larger cytoplasmic areas than the other 2 staining reactions. In the antral mucosa, a cell population with the same staining characteristics as mentioned above was seen, but 2 further cell populations were identified--one displaying FIF-argentaffin reactions but no serotonin immunoreactivity, and the other showing the opposite characteristics. At immunostaining, a discrepancy in the staining results between the 2 antisera was noted--a larger number of antral serotonin immunoreactive cells being demonstrated with the polyclonal than with the monoclonal antiserum; this discrepancy disappeared when the polyclonal antiserum was pretreated with C-terminal tetragastrin. A minor discrepancy in the number of stained cells was still observed between the use of immunostaining with monoclonal or with tetragastrin-pretreated polyclonal antiserum, and the use of the FIF-argentaffin reactions. The reason for this discrepancy is unclear.

Animals↗
PubMed1972

Pheochromocytoma.

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Adrenal Gland Neoplasms↗
PubMed1996

Similarities and differences in supporting and chromaffin cells in the mammalian adrenal medullae: an immunohistochemical study.

BACKGROUND: The adrenal medulla is a typical paraganglion, having the same origin as the sympathetic ganglia, and contains at least two types of parenchymal cells: chromaffin cells and supporting cells. We previously reported that the extent of cellular association of chromaffin cells with supporting cells was remarkably higher in noradrenaline (NA)-than in adrenaline (A)-cell regions in the adrenal medullae of the rat and pig. METHODS: Cryostat sections of adrenal medullae of nine mammalian species fixed with Zamboni fluid for 24 h were immunostained by ABC methods using antisera to S-100 protein and PNMT. RESULTS: The distribution patterns of A and NA cells in the adrenal medullae were classified into four types. In the chipmunk and rabbit, adrenomedullary chromaffin cells consisted of A cells. S-100-immunoreactive cells were present more frequently in NA- than in A-cell regions in seven species (rat, golden hamster, cat, dog, pig, ox, and horse). These cells sent out cytoplasmic processes and formed a network by immunoreactive elements among NA cells. The cell-association patterns of S-100-positive cells with NA cell were classified into three types. In A-cell regions, only a few S-100-positive cells were seen in most of the species, although the frequency of S-100-labeled cells were exceptionally high in the horse. CONCLUSIONS: The close association of supporting cells with NA cells was commonly found in the adrenal medulla in many mammalian species, irrespective of the proportions and distribution patterns of A cells and NA cells. On the other hand, species differences existed in details of the cellular association between supporting cells and NA cells.

Adrenal Medulla↗
PubMed1996

Activation of Fyn tyrosine kinase upon secretagogue stimulation of bovine chromaffin cells.

Adrenal medullary chromaffin cells derive from the neural crest during embryogenesis and differentiate into dedicated secretory cells that release catecholamines in response to acetylcholine in vivo or nicotinic agonists in vitro. Previous studies have indicated that tyrosine kinases participate in early secretagogue-induced events in these cells and are required for exocytosis. Abundant levels of the cytoplasmic tyrosine kinases, c-Src and c-Yes, have been detected in chromaffin cells, thereby implicating them as kinases relevant to these events. However, c-Src has been found to undergo a decrease in activity following secretagogue-stimulation, and c-Yes appears to exist in a constituitively low activity state, suggesting that other tyrosine kinases are involved. Furthermore, other members of the Src family of tyrosine kinases have been implicated as playing roles in secretion in a variety of cell types. Therefore, we sought to determine if other Src family members were present in chromaffin cells, and if so, to examine them for subcellular localization and changes in activity following treatment with nicotinic agonists. To this end, antibodies for Fyn, Lck, Lyn, and Fgr were assembled and used in immunoprecipitation, in vitro autokinase, and Western immunoblotting assays. Of these four kinases, only Fyn was found to be expressed at detectable levels. Differential centrifugation studies revealed that Fyn resides predominantly (> 95%) in the crude plasma membrane fraction and undergoes nicotinic-and carbachol-induced activation. This activation is reduced by the nicotinic antagonist, mecamylamine, is not elicited by muscarine, and is dependent upon the presence of extracellular Ca2+. These results suggest that Fyn is involved in signalling through the nicotinic receptor and may be one of the relevant kinases responsible for at least some of the tyrosine phosphorylations detected after stimulation.

Acetylcholine↗
PubMed1977

The histogenesis and development of pulmonary tumorlets.

A lung, which was surgically removed from a patient who had oat cell carcinoma, contained multiple tumorlets and showed extensive Kultschitsky-type cell proliferation of bronchial and bronchiolar mucosa. On the basis of light and electron microscopic observations, it is shown that pulmonary tumorlets arise from focal areas of bronchial and bronchiolar Kultschitsky cell proliferation which may advance to luminal obliteration. Involvement of the pulmonary parenchyma takes place by extension of these newly proliferated cells along the terminal branches of the bronchiolar tree or by penetration of the bronchial or bronchiolar wall; the latter process evokes a striking proliferation of connective tissue which forms the matrix in which the cells of some fully developed tumorlets are embedded. Because of striking morphologic similarities between tumorlets and spindle cell carcinoid tumors, and the proven origin of tumorlets from pulmonary Kultschitsky-type cells, it is suggested that the more complete and histogenetically acceptable term "carcinoid tumor-let" be used to distinguish this lesion from other forms of epithelial proliferations in the lung.

Carcinoid Tumor↗
PubMed1977

Malignant pheochromocytoma with features suggesting the Brown-Séquard syndrome. A case report.

A case of malignant pheochromocytoma arising from the abdominal preaortic chromaffin tissue is presented. Of particular note is that right hemiplegia associated with sensory disturbances, compatible with the Brown-Séquard syndrome, was an outstanding early clinical manifestation. The patient finally developed signs of complete transection of the spinal cord which was caused by metastasis of the tumor to the cervical spines. The neurological abnormalities observed in the present case were so unusual in pheochromocytoma as to lead initially a diagnosis of cord tumor. Autopsy findings well supported the clinical diagnosis. Cases like this have not been reported so far.

Adult↗
PubMed1983

A colonic adenocarcinoma with argentaffin cells. An immunoperoxidase study demonstrating the presence of numerous neuroendocrine products.

A well-differentiated colonic adenocarcinoma containing large numbers of gastrointestinal neuroendocrine cells is presented. The presence of neurosecretory granules was confirmed by electron microscopy. Immunocytochemistry showed large numbers of serotonin-containing tumor cells and lesser numbers of somatostatin, gastrin, motilin, secretin and neurotensin-containing cells. Some of these hormones are not normally present in the colon in significant numbers of cells. The presence of several cell types within a single tumor supports the concept that the normal epithelial cells of the gastrointestinal mucosa are derived from a common endodermal stem cell. There exists a spectrum of tumors ranging from the classical adenocarcinoma to the classical carcinoid, and this report identifies the position of this case within that spectrum.

Adenocarcinoma↗
PubMed1983

Mammary carcinoma with argyrophil cells.

In a series of 253 cases of carcinoma of the breast, nonargentaffin, argyrophil cells were seen among the tumor cells in 27 cases (10.7%). An electron microscopic examination in one such case revealed dense cored secretory granules surrounded by a limiting membrane within the cytoplasm of the argyrophil tumor cells. Tumors with argyrophil cells, particularly when these cells were abundant, histologically showed a uniform appearance of relatively small constituent cells with oval or round nuclei of a regular size, forming solid alveolar nests or sheets. In one of these tumors, a delicate vascular stroma separated the sheets of tumor cells to form a ribbonlike pattern, simulating the feature of a carcinoid tumor. This tumor, however, is preferably interpreted at present as a mammary carcinoma with features of a carcinoid tumor, because of an incomplete characterization of argyrophil granules in the tumor cells. Other tumors with argyrophil cells were examples basically of ordinarily featured invasive ductal carcinoma. In a search for the origin of these cells, 99 breasts with various noncancerous lesions were examined; however, these argyrophil cells were never detected in any component of these mammary tissues.

Adult↗