Receptor-receptor link in membranes revealed by ligand competition: example for dopamine D1 and D2 receptors.
An interaction or link between dopamine D1 receptors and dopamine D2 receptors was found by a ligand competition method, using [3H]raclopride to label dopamine D2 receptors and SCH 23390 to block dopamine D1 receptors. In the presence of endogenous or exogenous dopamine, SCH 23390 increased the binding of [3H]raclopride in post-mortem human striata homogenates or in tissue culture cells containing human dopamine D1 and D2 receptors. In order to reveal such intramembrane receptor-receptor interactions in general, therefore, it appears essential to add two agonists, one for each receptor, and then to block one of the receptors when measuring the binding of a ligand to the second receptor.
Seeman
P
P
Department of Pharmacology, University of Toronto, Ontario, Canada.
Sunahara
R K
RK
Niznik
H B
HB
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D008024:Ligands; D051379:Mice; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D004298:Dopamine