In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B.

ABSTRACT: Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, and non-peptide drugs are currently being developed to treat insomnia and narcolepsy. Yet, no light-regulated agents are available to reversibly control their activity. To meet this need, a photoswitchable peptide analogue of the endogenous neuroexcitatory peptide orexin-B was designed, synthesized, and tested in vitro and in vivo. This compound - photorexin - is the first photo-reversible ligand reported for orexin receptors. It allows dynamic control of activity in vitro (including almost the same efficacy as orexin-B, high nanomolar potency, and subtype selectivity to human OX₂ receptors) and in vivo in zebrafish larvae b

SUBMITTER: Prischich D 

PROVIDER: S-EPMC11335211 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature