Cannabinoids enhance gastric X/A-like cells activity.

Abstract

It has been reported that cannabinoids may cause overeating in humans and in laboratory animals. Although, endogenous cannabinoids and their receptors (CB1) have been found in the hypothalamus, and recently also in gastrointestinal tract, the precise mechanism of appetite control by cannabinoids remains unknown. Recently, ghrelin -a hormone secreted mainly from the stomach X/A-like cells was proposed to be an appetite stimulating agent. The aim of this study was the evaluation of the influence of a single ip injection of a stable analogue of endogenous cannabinoid -anandamide, R-(+)-methanandamide (2.5 mg/kg) and CP 55,940 (0.25 mg/kg), an exogenous agonist of CB1 receptors, on ghrelin plasma concentration and on ghrelin immunoreactivity in the gastric mucosa of male Wistar rats. Four hours after a single injection of both cannabinoids or vehicle, the animals were anaesthetized and blood was taken from the abdominal aorta to determinate plasma ghrelin concentration by RIA. Subsequently, the animals underwent resection of distal part of stomach. Immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. The attenuation of ghrelin-immunoreactivity of gastric mucosa, after a single injection of R-(+)-methanandamide and CP 55,940 was accompanied by a significant increase of ghrelin plasma concentration. These results indicate that stimulation of appetite exerted by cannabinoids may be connected with an increase of ghrelin secretion from gastric X/A-like cells.

The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease

“…A possibility is that they may act through CB 1 Rs on vagal terminals [24], on sympathetic nerve terminals [25], or indirectly through the modulation of gastrointestinal hormones. In particular, activation of CB 1 Rs in gastric cells induces secretion of ghrelin [26,27], an orexigenic hormone able to increase fat-taste perception [28] and the rewarding value of high-fat diets [29].…”

Endocannabinoids and Metabolic Disorders

“…Indeed, later studies have demonstrated that ghrelin requires functional CB 1 receptor signaling, which in turn may lead to the activation of AMP-activated protein kinase (AMPK), an intracellular fuel gauge known to mediate ghrelin's action within the hypothalamus (Kola et al 2008;Stark et al 2013). Furthermore, peripheral administration of anandamide or of synthetic CB 1 receptor agonists in rats increases plasma ghrelin levels and ghrelin secretion from the stomach (Zbucki et al 2008). Thus, a feed-forward mechanism exists where the ECS favors secretion of ghrelin and the latter in turn increases hypothalamic ECS activity, with the overall result of stimulating food intake and body weight gain.…”

The role of the endocannabinoid system in the neuroendocrine regulation of energy balance

“…Indeed, the administration of CB1 agonists or methanandamide (an anandamide analog) in rats increases plasma ghrelin levels and ghrelin secretion from gastric X/A-like cells (Zbucki et al, 2008).…”