Altered physical states of the membrane-bound acetylcholine receptor after affinity labelling.
The study of the interacstion of the bifunctional cholinergic ligand alpha-bromoacetylcholine with the membrane-bound acetylcholine receptor has allowed the identification of physically altered states of the receptor following affinity labelling. Depending on the integrity of a disulphide bond in the receptor, the ligand can either trigger the normal conversion of affinity states in unmodified membranes (apparent Kd's of approximately 0.5-1 microM and 5-10 nM in the low and high affinity states, respectively) or reversibly lock the reduced receptor in an agonist-insensitive state. Antagonists like d-tubocurarine release the receptor from this state, in accordance with in vivo observations. The integrity of a disulphide bond available for affinity acylation after reduction of the receptor appears to be essential for correct ligand discrimination and for the occurrence of ligand-induced state transitions of the membrane-bound receptor in vitro.
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000215:Acylation; D000345:Affinity Labels / Q000494:pharmacology*; D000818:Animals; D003039:Cobra Neurotoxin Proteins / Q000378:metabolism; D005399:Fishes; D005453:Fluorescence; D007700:Kinetics; D008024:Ligands; D008566:Membranes / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D014403:Tubocurarine / Q000494:pharmacology
D000345:Affinity Labels; D003039:Cobra Neurotoxin Proteins; D008024:Ligands; D011950:Receptors, Cholinergic; D000109:Acetylcholine; D014403:Tubocurarine