Molecular dissection of regulated secretory pathways in human gastric enterochromaffin-like cells: an immunohistochemical analysis

Citation
M. Hocker et al., Molecular dissection of regulated secretory pathways in human gastric enterochromaffin-like cells: an immunohistochemical analysis, HISTOCHEM C, 112(3), 1999, pp. 205-214
Citations number
37
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
HISTOCHEMISTRY AND CELL BIOLOGY
ISSN journal
09486143 → ACNP
Volume
112
Issue
3
Year of publication
1999
Pages
205 - 214
Database
ISI
SICI code
0948-6143(199909)112:3<205:MDORSP>2.0.ZU;2-7
Abstract
Enterochromaffin-like (ECL) cells regulate gastric acid secretion through v esicular release of histamine. Until now, the molecular machinery of human ECL cells involved in the formation and release of vesicles is largely unkn own. We analyzed tissue samples obtained from normal human gastric mucosa ( n=4) and ECLomas (n=5) immunohistochemically using the APAAP method or doub le immunofluorescence confocal laser microscopy. Human pheochromocytomas (n =5) were investigated in parallel and compared to ECL cells. Secretory path ways were characterized using antibodies specific for marker proteins of la rge dense-core vesicles (LDCVs; islet cell antigen 512, chromogranin A, pan creastatin, and vesicular monoamine transporter 2) and small synaptic vesic le (SSV) analogues (synaptophysin). Tissues were also analyzed for expressi on of the peptide hormone processing enzymes, carboxypeptidase E and prohor mone convertase 1, as well as the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, 25-kDa synaptosome-associate d protein (SNAP25), syntaxin, and syn aptobrevin. Immunoreactivity for mark ers of LDCVs and SSV analogues were detected in normal ECL cells and ECLoma s. Both tissues also showed expression of carboxypeptidase E and prohormone convertase 1. Analysis of vesicular SNARE (v-SNARE) and target membrane SN ARE (t-SNARE) proteins revealed the presence of SNAP25, syntaxin, and synap tobrevin in normal and neoplastic ECL cells. Our data suggest that ECL cell s possess the two vesicle types of regulated neuroendocrine secretory pathw ays, LDCVs and SSV analogues. Since ECL cells also contain typical SNARE pr oteins, the molecular machinery underlying secretory processes in this cell type appears to be identical to the secretory apparatus of neuroendocrine cells and neurons. In addition, our findings suggest that the secretory app aratus of ECL cells is maintained during neoplastic transformation.