Peripheral apelin-13 administration inhibits gastrointestinal motor functions in rats: The role of cholecystokinin through CCK1 receptor-mediated pathway

Abstract

Apelin is the endogenous ligand of the G protein-coupled receptor APJ. The APJ receptor is widely expressed in gastrointestinal (GI) tissues including stomach and small intestine. Apelin administration was shown to induce the release of cholecystokinin (CCK) which is a well-known alimentary hormone with its inhibitory actions on GI motor functions through CCK1 receptors on vagal afferent fibers. We investigated whether; (i) peripherally injected apelin-13 alters GI motor functions, (ii) apelin-induced changes are mediated by APJ receptor or CCK1 receptor and (iii) vagal afferents are involved in inhibitory effects of apelin. Solid gastric emptying (GE) and colon transit (CT) were measured, whereas duodenal phase III-like contractions were recorded in rats administered with apelin-13 (300μg/kg, ip). CCK1 receptor antagonist lorglumide (10mg/kg, ip) or APJ receptor antagonist F13A (300μg/kg, ip) was administered 30min prior to the apelin-13 injections. Vagal afferent denervation was achieved by systemic administration of vanilloid receptor agonist capsaicin (125mg/kg, sc). Apelin-13 administration significantly (p<0.01) increased the CCK level in portal venous plasma samples. Compared with vehicle-treated rats, apelin-13 significantly delayed both GE (p<0.001) and CT (p<0.01). Pretreatment of lorglumide or F13A completely abolished the apelin-13-induced inhibitory effects on GE and CT, moreover, apelin-13 was found ineffective in rats underwent afferent denervation. F13A administration alone significantly accelerated the basal CT. Apelin-13 noticeably disturbed the duodenal fasting motor pattern by impairing phase III-like contractions while increasing the amplitudes of phase II contractions which were prevented by pretreatment of lorglumide and capsaicin. Compared with vehicle-treated rats, lorglumide and capsaicin significantly (p<0.05) reduced the apelin-13-induced increases in phase II motility index. Peripherally administered apelin-13 inhibits GI motor functions through CCK-dependent pathway which appears to be mediated by CCK1 receptors on vagal afferents. Peripheral apelin might contribute to the motility changes occurred in postprandial period.