Cys-loop receptor (CLR)

Cys-loop receptors are a major superfamily of pentameric ligand-gated ion channels (pLGICs) that play a fundamental role in fast excitatory and inhibitory synaptic transmission throughout the central and peripheral nervous systems (IUPHAR/BPS Guide to Pharmacology). They are defined by a characteristic 13-amino acid loop in the extracellular N-terminal domain, closed by a disulfide bridge between two cysteine residues (PubMed: 25003714). This superfamily includes the nicotinic acetylcholine receptors (nAChR), gamma-aminobutyric acid type A receptors (GABA-A), glycine receptors (GlyR), and the serotonin type 3 receptor (5-HT3R) (UniProt). These receptors function as molecular switches that convert chemical signals—neurotransmitters—into electrical signals by opening an intrinsic ion-conducting pore upon ligand binding (PubMed: 15816835). Because of their central role in neural signaling, they are critical therapeutic targets for a variety of conditions, including anxiety, insomnia, epilepsy, and chemotherapy-induced nausea (StatPearls). Drugs targeting these receptors range from full agonists and antagonists to positive and negative allosteric modulators, which fine-tune channel activity (PubMed: 21496447).

Other names

Pentameric ligand-gated ion channelpLGICCys-loop ligand-gated ion channel superfamily

Agonism, antagonism, and allosteric modulation of ion channel opening to regulate cation or anion conductance across the cell membrane (PubMed: 15816835).