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
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.