A probe for octopamine receptors: synthesis of 2-[(4-azido-2,6-diethylphenyl)imino]imidazolidine and its tritiated derivative, a potent reversible-irreversible activator of octopamine-sensitive adenylate cyclase.
In order to develop an irreversible ligand for octopamine receptors, a highly potent azido-substituted 2-(phenyl-imino)imidazolidine (NC-5Z, 8) and its tritiated derivative (3H-NC-5Z, 11) have been designed and synthesized. Under reversible-binding conditions, NC-5Z is 50-100-fold more potent than octopamine in activating octopamine-sensitive adenylate cyclase in a variety of tissues. After photolysis, 3H-NC-5Z binds irreversibly to cell membranes, and this binding is reduced by preincubation with octopamine agonists and antagonists but not by norepinephrine, dopamine, serotonin, or histamine. NC-5Z should be useful both as a potent reversible octopamine agonist and as an affinity probe for characterizing and isolating octopamine-receptor proteins.
Nathanson
J A
JA
Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Kaugars
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism*; D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D048289:Imidazolidines; D009655:Octopamine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D017982:Receptors, Biogenic Amine; D014316:Tritium
D001386:Azides; D007093:Imidazoles; D048289:Imidazolidines; D011941:Receptors, Adrenergic; D017982:Receptors, Biogenic Amine; C027604:norsynephrine receptor; D014316:Tritium; C060351:NC 5Z; D009655:Octopamine; D000262:Adenylyl Cyclases