The ghrelin receptor GHSR has two efficient agonists in the lobe-finned fish Latimeria chalumnae

The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled receptor. Ghrelin, LEAP2, and GHSR are widely present from fishes to mammals. However, our recent study suggested that fish GHSRs have different binding properties to ghrelin: a GHSR from the lobe-finned fish Latimeria chalumnae (coelacanth) is efficiently activated by ghrelin, but GHSRs from the ray-finned fish Danio rerio (zebrafish) and Larimichthys crocea (large yellow croaker) have lost binding to ghrelin. Do fish GHSRs use another peptide as their agonist? In the present study we tested to two fish motilins from D. rerio and L. chalumnae because motilin is distantly related to ghrelin. In ligand binding and activation assays, the fish GHSRs from D. rerio and L. crocea displayed no detectable or very low binding to all tested motilins; however, the fish GHSR from L. chalumnae bound to its motilin with high affinity and was efficiently activated by it. Therefore, it seemed that motilin is not a ligand for GHSR in the rayfinned fish D. rerio and L. crocea, but is an efficient agonist for GHSR in the lobe-finned fish L. chalumnae, one of the closest fish relatives of tetrapods. The results of present study suggested that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes; however, this feature might be only preserved in some extant fishes with ancient evolutionary origins.

Automated summary

The present study found that the GHSRs of fish have different binding properties to ghrelin. The GHSRs of zebrafish and large yellow croaker have lost their binding ability to ghrelin, while the GHSR of the lobe-finned fish Latimeria chalumnae can efficiently bind to ghrelin. Instead of ghrelin, motilin is an efficient agonist for GHSR in Latimeria chalumnae. This suggests that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes, but this feature might only be preserved in some extant fishes with ancient evolutionary origins.