A GPCR is a protein that crosses the cell membrane seven times. When its ligand, a peptide hormone for example, binds to the outer part, the receptor changes shape and activates a G protein on the inner side. That G protein starts second messengers such as cyclic AMP or calcium, which amplify the signal.
Most research peptides act on GPCRs: the GLP-1, GIP, glucagon and amylin receptors; the GHRH and ghrelin receptors in the growth hormone axis; the melanocortin receptors (MC1R to MC5R); the oxytocin or kisspeptin receptors. A large share of the world's approved drugs target a GPCR.
After activation, the receptor is phosphorylated and recruits β-arrestins, which uncouple it from the G protein and can pull it inside the cell. This is the underlying mechanism of desensitisation and tolerance.
Understanding GPCR signalling explains phenomena that appear again and again in the peptide literature: loss of response with continuous exposure, differences between “biased” agonists and why pulsatility matters in some hormonal axes.
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Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).