Down-regulation of ghrelin receptors in the stomach delays gastric emptying in vagotomized rats

Ghrelin promotes gastric emptying and small intestinal transit when injected through central or peripheral channels in experimental animals. When the vagal nerve is cut off, the central effect of ghrelin is abolished, the peripheral effect is still observed. Furthermore, the function of ghrelin receptor expressing nerve cells in gastric muscle layers is affected. Expressional changes in ghrelin receptors may affect the effect of ghrelin. The effects of intraperitoneal administration of ghrelin (20, 40 and 80 mu g/kg) on gastric emptying were studied in control and vagotomized rats in vivo. The effects of ghrelin (0.01, 0.1, 0.5 and 1.0 mu mol/L) on the contraction force of smooth muscle strips from the stomach were studied in vitro. Ghrelin receptor expression was studied in gastric layers by means of immunohistochemistry. Ghrelin dose-dependently increased gastric emptying in control and model rats. In addition, ghrelin enhanced smooth muscle strip contraction induced by carbachol. Ghrelin receptor expression in stomach smooth muscle layers was down-regulated in model rats. Downregulation of growth hormone secretagogue receptor 1a in gastric smooth muscle layers, which affected the effects of ghrelin, may be one of the mechanisms behind delayed gastric emptying after vagotomy.