Effect of reserpine on the generation of the chromogranin A-derived neuropeptide WE-14 in rat oxyntic mucosa

Summary, in English

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 oxymic 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.

• Author: JG Quinn; WJ Curry; Per Norlén
• Department/s: Division of Clinical Chemistry and Pharmacology
• Publishing year: 2005
• Language: English
• Pages: 1-6
• Publication/Series: Regulatory Peptides
• Volume: 124
• Issue: 1-3
• Links: http://dx.doi.org/10.1016/j.regpep.2004.06.028
• Document type: Journal article
• Publisher: Elsevier
• Topic: Cell and Molecular Biology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1873-1686