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Submitted on August 26, 2003
Accepted on November 18, 2003
1 Department of Surgery, Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, TX; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK
* To whom correspondence should be addressed. E-mail: ggreeley{at}utmb.edu.
Apelin is a recently discovered peptide that is the endogenous ligand for the APJ receptor. The aim of this study was to characterize apelin expression (mRNA levels) in the rat gastrointestinal (GI) tract and pancreas, to localize distribution of apelin peptide containing cells in the stomach by immunohistochemistry (IHC), to characterize the ontogeny of gastric apelin expression and peptide, and the influence of apelin on gastric cell proliferation in vitro. Additionally, the effect of apelin on cholecystokinin (CCK) secretion, and the involvement of mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and changes in [Ca2+]i in apelin-induced CCK secretion in vitro were examined. Northern analysis showed a maximal apelin expression in the stomach with a lower expression level in the intestine. Apelin expression was not detected in the pancreas. IHC revealed abundant apelin positive cells in the glandular epithelium of the stomach. The ontogeny study showed a higher apelin expression in the fetal and postnatal rat stomachs when compared with the adult stomach. In contrast to apelin expression, apelin peptide was not detected in the rat stomach until 20 days of age and then increased progressively with age. Apelin was shown to stimulate gastric cell proliferation in vitro. Apelin also stimulated CCK secretion from a murine enteroendocrine cell line (STC-1); apelin-stimulated CCK secretion is mediated through MAPK but not by [Ca2+]i signaling. Together, these data indicate that apelin is an important new stomach peptide with a potential physiologic role in the GI tract.
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