Gbahou et al. “Design and validation of the first cell-impermeant melatonin receptor agonist.” British Journal of Pharmacology (2017).
The paradigm that GPCRs are able to prolong or initiate cellular signalling through intracellular receptors recently emerged. Melatonin binds to G protein‐coupled MT1 and MT2 receptors. In contrast to most other hormones targeting GPCRs, melatonin and its synthetic analogues are amphiphilic molecules easily penetrating into cells, but the existence of intracellular receptors is still unclear mainly due to a lack of appropriate tools.
Read the full paper here: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13856