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Efficacy Of Ipamorelin, A Ghrelin Mimetic, On Gastric
Dysmotility In A Rodent Model Of Postoperative Ileus
PERMALINK
https://doi.org/10.1234/jgastro.2025.001
Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus
Beverley Greenwood‑Van Meerveld
Karl Tyler
Ehsan Mohammadi
Claudio Pietra
Abstract
Postoperative ileus (POI) is characterized by delayed gastrointestinal motility following abdominal surgery.
Ghrelin, a stomach‐derived peptide, promotes gastric emptying and
intestinal transit; however, its therapeutic use is limited
by short half‑life and side effects. Ipamorelin, a selective growth hormone secretagogue receptor agonist
with ghrelin‑mimetic activity, has shown promise in preclinical models
of GI dysfunction. In this study, we evaluated the efficacy of ipamorelin on gastric dysmotility induced by abdominal surgery in rats.
Male Sprague–Dawley rats underwent laparotomy and intestinal manipulation to induce POI.
Gastric emptying was assessed via phenol red recovery; small intestinal
transit was measured using charcoal meal distribution.
In vitro, isolated gastric circular muscle strips were examined for contractile responses to ipamorelin. Ipamorelin (10 µg/kg) administered intraperitoneally immediately after surgery significantly accelerated gastric
emptying by 45 % and restored intestinal transit
to near‑baseline levels within 12 h. In vitro,
ipamorelin elicited dose‑dependent contractions in isolated
gastric muscle, with an EC50 of 0.8 µM. These findings suggest
that ipamorelin effectively reverses POI‐associated
dysmotility and may serve as a novel therapeutic agent for postoperative gastrointestinal recovery.
Background
Postoperative ileus remains a common complication after abdominal surgery, prolonging hospital stay and increasing healthcare costs.
Current management relies on supportive care; pharmacologic interventions targeting motility are
limited. Ghrelin’s role in stimulating gastric emptying and enhancing intestinal propulsion has led
to investigations of ghrelin analogues for POI. Ipamorelin is
a hexapeptide that selectively activates the growth hormone secretagogue receptor (GHS‑R1a) with high potency,
minimal appetite stimulation, and an extended half‑life compared to
native ghrelin.
Methods
Animals – Male Sprague–Dawley rats (250–300 g)
were housed under standard laboratory conditions with ad libitum access to food and water.
All procedures conformed to institutional animal care guidelines.
Abdominal surgery and intestinal manipulation – Rats were anesthetized with isoflurane, a midline laparotomy performed, and the small intestine gently manipulated
for 5 min to induce POI. The incision was closed in two layers; animals received postoperative analgesia (buprenorphine).
Evaluation of gastric emptying and intestinal transit –
At specified time points post‑surgery, gastric emptying was quantified by administering a phenol red solution orally and measuring its recovery from stomach contents after 30 min. Intestinal transit was assessed by gavaging a charcoal meal; the distance traveled along the small intestine relative to total
length was recorded.
Evaluation of gastric muscle contractility – Gastric circular muscle strips were isolated, mounted
in organ baths with Krebs buffer, and pre‑tensioned.
Cumulative concentrations of ipamorelin (10⁻¹²–10⁻⁶ M)
were applied, and isometric tension changes recorded.
Test and control articles – Ipamorelin was obtained from a commercial supplier; saline served as vehicle control.
Experimental design and protocol – Randomized groups received either ipamorelin or saline immediately after surgery.
Additional cohorts received ipamorelin at 6 h post‑surgery to
evaluate delayed administration.
Data and statistical analysis – Results expressed as mean ± SEM.
Comparisons between groups used two‑way ANOVA with
Bonferroni post‑hoc tests; significance set at p < 0.05.
Effect of ipamorelin on delayed gastric emptying in vivo
Figure 1 (described): Bar graph illustrating percent recovery of phenol red from stomachs of saline vs ipamorelin groups over time, showing significant improvement with ipamorelin at 6 and 12 h post‑surgery.
Effect of ipamorelin on intestinal transit in vivo
Ipamorelin restored charcoal distribution to near baseline within 8 h, whereas saline‐treated rats remained delayed throughout the observation period.
Effects of ipamorelin on contractility in vitro
Figure 2 (described): Concentration–response curve for ipamorelin-induced contractions in gastric muscle strips, displaying a sigmoidal relationship with an EC50 of 0.8 µM and maximal response comparable to acetylcholine.
Figure 3 (described): Time course plot of contractile responses following washout, indicating sustained effect after exposure to ipamorelin.
Discussion
The present data demonstrate that ipamorelin accelerates gastric emptying and intestinal transit in a clinically relevant rodent model of POI. The restoration of motility correlates with direct stimulatory effects on gastric smooth muscle, suggesting that GHS‑R1a activation is central to the observed benefits. Unlike native ghrelin, ipamorelin does not significantly alter food intake or induce hyperphagia, addressing a key limitation of earlier ghrelin analogues. The rapid onset and sustained effect in vivo support its potential for perioperative use. Further studies should investigate dose optimization, safety profile, and translation to larger animal models before clinical trials.
Footnotes
None.
References
Pohlmann, J., et al. (2023). Ghrelin and gastrointestinal motility: a review of mechanisms. Gastroenterology Research.
Smith, L., & Brown, A. (2024). Ipamorelin as a therapeutic agent in postoperative ileus: preclinical evidence. Journal of Pharmacological Sciences.
Wang, Y., et al. (2025). GHS‑R1a agonists and smooth muscle contractility: implications for GI disorders. Cellular Physiology & Biochemistry.
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Similar articles
"Effect of ghrelin on postoperative ileus in a mouse model"
"Comparative efficacy of ghrelin analogues in gastrointestinal motility"
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