title: Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.
abstract: Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway.
authors.affiliation: Akdeniz University Faculty of Medicine Department of Physiology, Antalya, Turkey; and mehmetbulbul@akdeniz.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bülbül
authors.affiliation: Akdeniz University Faculty of Medicine Department of Physiology, Antalya, Turkey; and.
authors.forename: V Nimet
authors.initials: VN
authors.lastname: İzgüt-Uysal
authors.affiliation: Akdeniz University Faculty of Medicine Department of Physiology, Antalya, Turkey; and.
authors.forename: Osman
authors.initials: O
authors.lastname: Sinen
authors.affiliation: Akdeniz University Faculty of Medicine Department of Physiology, Antalya, Turkey; and.
authors.forename: İlknur
authors.initials: İ
authors.lastname: Birsen
authors.affiliation: Akdeniz University Faculty of Medicine Department of Histology and Embryology, Antalya, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Tanrıöver
mesh_terms: D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D003106:Colon / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005746:Gastric Emptying; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000503:physiopathology*; D005772:Gastrointestinal Transit; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D019518:Postprandial Period; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D016760:Proto-Oncogene Proteins c-fos; D043562:Receptors, G-Protein-Coupled; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: apelin; corticotropin releasing factor; gastrointestinal motility; microdialysis; stress