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

Abstract

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 (300 μg kg −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.

Circumventricular Organ Apelin Receptor Knockdown Decreases Blood Pressure and Sympathetic Drive Responses in the Spontaneously Hypertensive Rat

“…Apelin injected i.p. has been shown to increase hypothalamic ( Higuchi et al, 2007 ) and cerebrospinal fluid ( Sinen and Bülbül, 2021 ) apelin levels, and to activate c-Fos in the PVN ( Takayama et al, 2008 ) and CVO ( Sinen and Bülbül, 2021 ), indicating that systemic apelin may be able to cross the BBB to stimulate central neurons. Based on studies of many peptides it is unlikely that polar substances such as apelin-13 and larger apelin fragments would cross the BBB by diffusion but may enter the brain parenchyma via carrier-mediated and/or receptor mediated transport ( Lee and Jayant, 2019 ).…”

Sex-related differences in anxiety in experimental functional dyspepsia induced by chronic stress

“…After the behavioral experiments, animals underwent overnight fasting, as previously reported (18,19). Overnight fasting rats were given pre-weighed pellets (1.6 g).…”