Chemical modification reveals involvement of tyrosine in ligand binding to dopamine D1 and D2 receptors.
The effect of tyrosine-alkylating agents on the ligand-binding properties of bovine striatal dopamine D1 and D2 receptors was investigated. The tyrosine-alkylating agents, p-nitrobenzenesulphonylfluoride (pNBSF) and tetranitromethane (TNM) caused a time-and dose-dependent loss of the binding of [3H]SCH-23390 and [3H]spiroperidol, ligands specific for dopamine D1 and D2 receptors, respectively. The two dopamine receptors, however, showed a differential sensitivity to inactivation by these agents. The mechanism of inhibition of the two receptors appears to be complex as treatment of membranes with pNBSF and TNM resulted in a decrease of both the Kd and the Bmax of ligand binding. Spiroperidol almost completely protected the TNM-induced inhibition of [3H]spiroperidol binding to dopamine D2 receptors whereas SCH-23390 afforded only partial protection of the [3H]SCH-23390 binding by TNM suggesting that more than one tyrosine groups may be involved in the D1 receptor binding activity.
Srivastava
L K
LK
Department of Psychiatry, Science Faculty of Health Sciences, McMaster University, Hamilton, Ontario Canada.
Mishra
R K
RK
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001665:Binding Sites; D002417:Cattle; D003342:Corpus Striatum / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009578:Nitrobenzenes / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013774:Tetranitromethane / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
D000477:Alkylating Agents; D001552:Benzazepines; D008024:Ligands; D009578:Nitrobenzenes; D011954:Receptors, Dopamine; C034442:4-nitrobenzenesulfonyl fluoride; D014443:Tyrosine; D013134:Spiperone; D013774:Tetranitromethane; D004229:Dithiothreitol