[3H]methylcarbamylcholine, a new radioligand for studying brain nicotinic receptors.
A new radioligand, [3H]methylcarbamylcholine, has been developed for the study of the nicotinic cholinergic and nicotine-like binding sites in rat brain membranes. A Scatchard analysis with the radioligand yielded a Kd of 1.1 X 10(-9) M and a Bmax of 4.0 X 10(-14) moles/mg protein which compares with a lower affinity site for (-)-[3H]nicotine having a Kd of 3 X 10(-9) M and a Bmax of 2 X 10(-14) moles/mg. Comparable values for the Kd were obtained from a Hill plot and from calculations based on rate constants for association and dissociation. A comparison of the binding affinities of various nicotine analogues, nicotinic cholinergic agents, and other neurotropic agents revealed a close similarity between the two radioligands, with the exception that quaternization of nicotine or carbamate esters increased affinity by at least an order of magnitude with [3H]methylcarbamylcholine and resulted in a comparable decrease in affinity with [3H]nicotine as the ligand. The binding of [3H]methylcarbamylcholine, like [3H]nicotine, was not displaceable by muscarinic cholinergic antagonists. It was concluded that, although [3H]methylcarbamylcholine and [3H]nicotine bind to a common receptor in brain, the functional and chemical characteristics of the receptor(s) differ in some respects from peripheral nicotinic cholinergic receptors.
D000818:Animals; D001923:Brain Chemistry; D002217:Carbachol / Q000031:analogs & derivatives*; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009538:Nicotine / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000032:analysis*; D014316:Tritium
D008024:Ligands; D011619:Psychotropic Drugs; D011978:Receptors, Nicotinic; D014316:Tritium; C053765:N-methylcarbamylcholine; D009538:Nicotine; D002217:Carbachol; D002794:Choline