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.
Bidirectional cross-talkGhrelin activated the motilin (gut motility) receptor AND motilin activated the ghrelin (GH) receptor — two peptide systems are molecularly linked
What the researchers 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.
Why it matters
This cross-reactivity explains why GH secretagogues cause gut side effects (nausea, motility changes) and suggests motilin receptor drugs could affect GH release.
How the study worked
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.
What this study cannot tell us
In-vitro cross-reactivity. The physiological significance of motilin-GHS-R activation at endogenous concentrations is uncertain.
How to read the evidence
Preliminary in-vitro evidence demonstrating clear bidirectional receptor cross-reactivity between two peptide systems.
When this study was published
Published in 2003. The ghrelin-motilin receptor family relationship has been confirmed and influences drug design.
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.
Questions still open
- 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?
Common questions
Why do GH peptides affect the gut?
Could gut drugs affect growth hormone?
Read the original research
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
Citation
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.