The role of autonomic pathways in peripheral apelin-induced gastrointestinal dysmotility: involvement of the circumventricular organs.

Abstract

What is the central question of this study? Are central autonomic pathways and circumventricular organs involved in apelin-induced inhibition of gut motility? What is the main finding and its importance? Peripherally administered apelin-13 inhibits gastric and colonic motor functions through sympathetic and parasympathetic autonomic pathways, which seems to be partly mediated by the apelin receptor in circumventricular organs. Peripheral administration of apelin-13 has been shown to inhibit gastrointestinal (GI) motility, but the relevant mechanisms are incompletely understood. This study aimed to investigate (i) whether the apelin receptor (APJ) is expressed in circumventricular structures involved in autonomic functions, (ii) whether they are activated by peripherally administered apelin, (iii) the role of autonomic pathways in peripheral exogenous apelin-induced GI dysmotility, and (iv) the changes in apelin levels in the extracellular environment of the brain following its peripheral application. Ninety minutes after apelin-13 administration (300μgkg-1 , i.p.), gastric emptying (GE) and colon transit (CT) were measured in rats that underwent parasympathectomy and/or sympathectomy. Plasma and cerebrospinal fluid (CSF) samples were also collected from another group of rats that received apelin-13 or vehicle injection. The immunoreactivities for APJ and c-Fos in circumventricular organs (CVOs) were evaluated by immunohistochemistry. Compared with vehicle-treated rats, GE and CT were inhibited significantly by apelin-13 treatment, and were completely restored in animals that underwent the combination of parasympathectomy and sympathectomy and sympathectomy alone, respectively. Apelin concentrations were elevated in both plasma and CSF following peripheral administration of apelin-13. APJ expression was detected in area postrema (AP), subfornical organ and organum vasculosum of lamina terminalis, and c-Fos expression was observed in response to apelin injection. Apelin-induced c-Fos expression in AP was partially attenuated by pretreatment with the cholecystokinin-1 receptor antagonist lorglumide, whereas it was completely abolished in vagotomized rats. The present data suggest that APJ in CVOs could indirectly contribute to the inhibitory action of peripheral apelin on GI motor functions.