Pseudoallosteric modulation by (+)-MK801 of NMDA-coupled phencyclidine binding sites.
Two high affinity phencyclidine (PCP) binding sites, labelled by [3H] 1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP), have been identified in guinea pig brain, with one site coupled to the N-methyl-D-aspartate (NMDA) receptor (site 1) and the other site associated with the dopamine reuptake carrier complex (site 2). In this study, PCP enhanced the dissociation of [3H]TCP from PCP site 1 and site 2, while (+)-MK801 only enhanced dissociation of [3H]TCP from PCP site 1. Although additional studies will be required to determine the exact mechanism(s) of these effects, these data demonstrate that the interactions of PCP with both site 1 and site 2 are more complex than previously appreciated.
Reid
A A
AA
Unit on Receptor Studies, NIDDK, NIH Bethesda, MD 20892.
Monn
J A
JA
Jacobson
A E
AE
Rice
K C
KC
Rothman
R B
RB
D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D008024:Ligands; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine
D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine