Study summary · research use only
Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this rat study, ipamorelin, a synthetic peptidomimetic acting on the ghrelin receptor, was tested for its effect on gastric emptying in a model of gastroparesis induced by laparotomy and intestinal manipulation. Fasted adult male rats received ipamorelin (0.014-0.14 µmol/kg) or vehicle intravenously after surgery, and gastric emptying was measured 15 minutes after intragastric technetium-99m sulfur colloid. Surgery was associated with delayed gastric emptying, with 78% ± 5% of the meal remaining in vehicle-treated rats; ipamorelin (0.014 µmol/kg) was associated with 52% ± 11% remaining, versus 44% ± 6% in nonsurgical controls (P < 0.05 vs vehicle). In isolated gastric fundus tissue, ipamorelin (1 µM) reversed reduced contractile responses to acetylcholine and electrical stimulation seen after surgery. The authors suggest ipamorelin accelerates gastric emptying via a ghrelin receptor mechanism.
Abstract
Delayed gastric emptying is a common disorder with few effective therapeutic options. The goal of this study was to investigate whether ipamorelin, a synthetic peptidomimetic that acts on the ghrelin receptor, accelerates gastric emptying in a rodent model of gastroparesis induced by abdominal surgery and intestinal manipulation. Fasted adult male rats were subjected to laparotomy and intestinal manipulation. Following the surgery rats received ipamorelin (0.014-0.14 µmol/kg) or vehicle control via intravenous administration. Gastric emptying was measured by the percent of total recovered radioactivity remaining in the stomach 15 minutes after intragastric gavage of 1.5 mL of (99m)Tc (technicium-99m) sulfur colloid in 0.5% methylcellulose. In a separate group of rats subjected to laparotomy and intestinal manipulation, the gastric fundus was isolated and tissue segments were suspended in an organ bath to assess the effect of ipamorelin (1 µM) on gastric smooth muscle contractility induced by acetylcholine and electrical field stimulation. Abdominal surgery caused a delay in gastric emptying with 78% ± 5% of the meal remaining in the stomach in vehicle controls. Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%. Following abdominal surgery and intestinal manipulation, isolated preparations of gastric smooth muscle exhibited a marked inhibition of acetylcholine and electrical field stimulation-induced contractile responses, which were reversed by ipamorelin and ghrelin. These results suggest that ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.
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