Chromogranin A, B and C immunoreactivities of mammalian endocrine cells

Rindi, Guido; Buffa, Roberto; Sessa, Fausto; Tortora, O.; Solcia, Enrico

doi:10.1007/bf00508649

Cited by 256 publications

(37 citation statements)

References 31 publications

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“…Confirming previous findings our study showed that gastrin, CgA, and CgB immunoreactivities colocalized in identical G-cells (17,18,27); typically, these immunoreactivities varied markedly within the G-cell population. Basically, two reasons may explain the intercellular variations of immunoreactivities in a given tissue section: (i) existence of molec- ular variants (precursor forms and breakdown products) of gastrin, CgA, and CgB that crossreact differently with the corresponding antiserum; (ii) intercellular differences in the amount of gastrin, CgA, and CgB.…”

Section: Discussionsupporting

confidence: 91%

Mutual relationships between chromogranins A and B and gastrin in individual gastrin cells.

Cetin

Bargsten

Grube

1992

Proc. Natl. Acad. Sci. U.S.A.

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The chromogranins A and B (CgA and CgB, respectively), originally detected in the adrenal medulla, are present in various endocrine organs. Remarkably, their immunoreactivities vary among different endocrine cell types and also within a given endocrine cell population. With densitometric techniques at the cellular level, individual gastrin cells (n = 318) from guinea pig antral mucosa were studied to measure their content of immunoreactive CgA, CgB, and gastrin. The composition of these secretory proteins in individual gastrin cells varied considerably but with predictable components. Statistical evaluation of the data showed that immunoreactivities for gastrin and CgA correlated negatively in these cells; CgA and CgB immunoreactivities also correlated inversely. On the other hand, immunoreactivities for gastrin and CgB exhibited a high positive correlation. The mutual relationships between gastrin, CgA, and CgB suggest that under physiological conditions biosynthetic pathways of these secretory constituents are linked to each other in individual gastrin cells.The chromogranins (Cgs) consist of, at least, three acidic glycoproteins-Cg A (CgA), Cg B (CgB), and secretogranin II (l)-colocalized with secretory peptides or amines in secretory granules of neuroendocrine cells (2). In chromaffin cells, these proteins are probably involved in organizing the granule matrix (3) and in "sorting" peptides into the regulated secretory pathway (4-6). Moreover, the Cgs may serve as prohormones for bioactive peptides (7,8).Regulation of the biosynthesis of these secretory proteins has been studied under various experimental conditions (9-12) but has not been fully elucidated in cells under physiological conditions. Moreover, despite a common fate of the Cgs and resident peptide hormones or neuropeptide precursors demonstrated by bio-and immunochemical techniques in cell cultures (9,13,14), the interrelationships between the various secretory constituents remain largely unknown in individual endocrine cells under in situ conditions. Recent investigations have shown that the immunoreactivities for the Cgs vary not only among endocrine organs (9-11) but also among different endocrine cell types (15-18). Finally, even within a given endocrine cell population cellto-cell differences of immunoreactivities for the Cgs and for the peptide hormone have been demonstrated (15)(16)(17)(18)(19).We used the guinea pig gastrin cell (G-cell) population to investigate the intercellular variations of immunoreactivities for gastrin, CgA, and CgB and their quantitative interrelations in individual G-cells by densitometric immunohistochemistry and statistical analysis.We report here that significant relationships exist between gastrin, CgA, and CgB, indicating that the biosynthesis and/or storage of these secretory constituents are linked together in individual cells. MATERIALS AND METHODSTissue and Tissue Preparation. Small specimens of the gastric antral mucosa of guinea pigs (n = 8; food and water ad libitum) were snap-frozen in Freon 22...

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Section: Discussionsupporting

confidence: 91%

Mutual relationships between chromogranins A and B and gastrin in individual gastrin cells.

Cetin

Bargsten

Grube

1992

Proc. Natl. Acad. Sci. U.S.A.

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“…The relatively poor affinity for histamine of VMAT2 may not be critical in the histamine-rich ECL which, at least in rats, is essentially devoid of serotonin and catecholamines (Hakanson, 1970;Rubin & Schwartz, 1983, 1984 (Dimaline & Sandvik, 1991;Swarovsky et al 1994). In addition, we observed a twofold increase in the mRNA encoding CGA, which is located in rat ECL cells (Rindi, Buffa, Sessa, Tortora & Solcia, 1986;Grube, Bargsten, Cetin & Yoshie, 1989) and which is thought to play a role in the formation and stabilization of secretory granules (Wiedenmann & Huttner, 1989;Helle, 1990 …”

Section: Discussionmentioning

confidence: 76%

Expression and regulation of a vesicular monoamine transporter in rat stomach: a putative histamine transporter.

Dimaline

Struthers

1996

The Journal of Physiology

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1. Vesicular monoamine transporters (VMATs) translocate monoamines from the cytoplasm into secretory vesicles of endocrine cells and neurones, but they have limited affinity for histamine, and the identity of the vesicular transporter for this monoamine is uncertain. The aims of the present study were to characterize VMAT representatives in rat gastric corpus, and to determine if their expression was regulated by factors that modulate histamine biosynthesis. 2. Polymerase chain reaction (PCR) cloning using oligonucleotide primers to DNA sequences conserved within the VMAT family provided evidence for VMAT2, but not VMAT1 in rat gastric corpus. Northern analysis using a VMAT2 complementary RNA probe revealed a single 4 kb mRNA species in corpus endocrine cells.3.. In rats treated for up to 5 days with the H+-K+-ATPase inhibitor omeprazole, VMAT2, histidine decarboxylase and chromogranin A mRNA abundance in gastric corpus, and plasma gastrin concentrations increased progressively. Omeprazole also elevated VMAT2 expression in rats fasted for 48 h, but fasting alone, or refeeding fasted animals had no effect. 4. The results are consistent with a role for VMAT2 in the transport of histamine into enterochromaffin-like cell secretory vesicles, and with upregulation of the transporter to accommodate the increased histamine biosynthesis and secretion that accompanies achlorhydria.

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“…synaptophysin and chromogranin A, which are components of small synaptic-like vesicles, and large dense-core vesicles, respectively (Rindi et al 1986, Wiedenmann et al 1986). Furthermore, GEPNETs are derived from progenitor cells in the intestinal crypts or pancreatic ducts, and consequently express epithelial markers, e.g.…”

Section: Discussionmentioning

confidence: 99%

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

Hofving¹,

Arvidsson²,

Almobarak³

et al. 2018

Endocrine-Related Cancer

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Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.

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Chromogranin A, B and C immunoreactivities of mammalian endocrine cells

Cited by 256 publications

References 31 publications

Mutual relationships between chromogranins A and B and gastrin in individual gastrin cells.

Mutual relationships between chromogranins A and B and gastrin in individual gastrin cells.

Expression and regulation of a vesicular monoamine transporter in rat stomach: a putative histamine transporter.

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

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