Effect of reserpine on the generation of the chromogranin A-derived neuropeptide WE-14 in rat oxyntic mucosa.
WE-14, a post-translational product of the neuroendocrine protein chromogranin A (CgA), is generated in distinct subpopulations of endocrine cells. The objective of this study was to investigate the generation of WE-14 in the endocrine cell types of the oxyntic mucosa of the stomach, after treatment with reserpine, an irreversible inhibitor of vesicular monoamine uptake 2 (VMAT2). Reserpine (10 mg/kg) was administered subcutaneously and tissue analysed 1, 3, 5 and 18 h following treatment. The oxyntic mucosa was analysed immunohistochemically employing a site-specific WE-14 antiserum, a region-specific CgA antiserum and an antiserum against histidine decarboxylase (HDC), a marker of the histamine-producing ECL cells in the oxyntic mucosa. The number of oxyntic endocrine cells exhibiting WE-14 immunostaining increased more than 100-fold 18 h after reserpine administration relative to vehicle treated controls. Double immunostaining with HDC revealed that most, but not all, of the WE-14 positive cells were ECL cells. These results suggest that reserpine has the ability to influence the post-translational processing of CgA to generate WE-14 in rat stomach ECL cells, presumably as a consequence of reduced VMAT2-driven accumulation of histamine.
Quinn
J G
JG
Ophthalmology and Vision Science Research Centre, Institute of Clinical Science, Queen's University Belfast, Grosvenor Road, Belfast, BT12 6BA, Northern Ireland, United Kingdom.
Curry
W J
WJ
Norlén
P
P
D000595:Amino Acid Sequence; D000818:Animals; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D016415:Sequence Alignment
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C475441:WE14 protein, rat; C506153:chromogranin A, rat; D012110:Reserpine; D006640:Histidine Decarboxylase