Ghrelin and GHRP-6 Cross-React With the Motilin Receptor, Linking GH and Gut Motility

Ghrelin and GHRP-6 activated the motilin receptor (which controls gut contractions) and vice versa, revealing cross-talk between the GH secretagogue and gut motility receptor systems.

Depoortere, Inge et al.·The Journal of pharmacology and experimental therapeutics·2003·Preliminary Evidencein-vitro
RPEP-00810In VitroPreliminary Evidence2003RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
in-vitro
Evidence
Preliminary Evidence
Sample
Not reported

What This Study Found

Bidirectional cross-reactivity between ghrelin/GHRP-6 and the motilin receptor was demonstrated: ghrelin activated the motilin receptor and motilin activated GHS-R, linking GH regulation and gut motility at the receptor level.

Key Numbers

How They Did This

In-vitro receptor pharmacology. Ghrelin, GHRP-6, and motilin tested on cells expressing either GHS-R or motilin receptor. Binding and functional activation measured for both ligand-receptor combinations.

Why This Research Matters

This cross-reactivity explains why GH secretagogues cause gut side effects (nausea, motility changes) and suggests motilin receptor drugs could affect GH release.

The Bigger Picture

The body's GH and gut motility systems evolved from a common ancestor. Their receptor cross-reactivity means targeting one inevitably affects the other — important for drug development.

What This Study Doesn't Tell Us

In-vitro cross-reactivity. The physiological significance of motilin-GHS-R activation at endogenous concentrations is uncertain.

Questions This Raises

  • ?Do motilin receptor drugs (erythromycin) affect GH release?
  • ?Could selective GHS-R agonists avoid motilin receptor activation?
  • ?Does the cross-reactivity contribute to ghrelin's gut effects?

Trust & Context

Key Stat:
Bidirectional cross-talk Ghrelin activated the motilin (gut motility) receptor AND motilin activated the ghrelin (GH) receptor — two peptide systems are molecularly linked
Evidence Grade:
Preliminary in-vitro evidence demonstrating clear bidirectional receptor cross-reactivity between two peptide systems.
Study Age:
Published in 2003. The ghrelin-motilin receptor family relationship has been confirmed and influences drug design.
Original Title:
Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum.
Published In:
The Journal of pharmacology and experimental therapeutics, 305(2), 660-7 (2003)
Database ID:
RPEP-00810

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Why do GH peptides affect the gut?

Because ghrelin and GH secretagogues cross-react with the motilin receptor — the receptor that controls stomach and intestinal contractions. This molecular overlap means GH drugs inevitably have gut effects.

Could gut drugs affect growth hormone?

Potentially. Motilin activates the ghrelin receptor, so prokinetic drugs (which boost gut motility through motilin-like mechanisms) could theoretically affect GH release.

Read More on RethinkPeptides

Cite This Study

RPEP-00810·https://rethinkpeptides.com/research/RPEP-00810

APA

Depoortere, Inge; Thijs, Theo; Thielemans, Leen; Robberecht, Patrick; Peeters, Theo L. (2003). Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum.. The Journal of pharmacology and experimental therapeutics, 305(2), 660-7.

MLA

Depoortere, Inge, et al. "Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum.." The Journal of pharmacology and experimental therapeutics, 2003.

RethinkPeptides

RethinkPeptides Research Database. "Interaction of the growth hormone-releasing peptides ghrelin..." RPEP-00810. Retrieved from https://rethinkpeptides.com/research/depoortere-2003-interaction-of-the-growth

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.