Competitive interactions at [3H]1,3-di(2-tolyl)guanidine (DTG)-defined sigma recognition sites in guinea pig brain.
In saturation binding experiments, (+)pentazocine, (+)3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), haloperidol and rimcazole did not inhibit the binding of [3H]DTG in a purely competitive fashion. Although Scatchard analysis indicated that [3H]DTG bound to a single site, the inhibition curves of some, but not all, reference compounds exhibited Hill coefficients of less than 0.8. The Scatchard data were consistent with a model of hyperbolic competitive inhibition of binding to the [3H]DTG-defined sigma site, although other possibilities such as negative cooperativity or binding to two sites cannot be definitively excluded. Compounds from numerous pharmacological and structural classes inhibited the binding of [3H]DTG, suggesting that interactions of [3H]DTG with other receptors may have confounded the Scatchard analysis of the binding of [3H]DTG to sigma recognition sites.
Department of Enzymology and Receptor Biochemistry, Sterling Winthrop Pharmaceuticals Research Division, Malvern, PA 19355-1314.
D L
DL
DeHaven-Hudkins
L C
LC
Fleissner
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism; D001667:Binding, Competitive; D002227:Carbazoles / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism; D006146:Guanidines / Q000378:metabolism*; D006168:Guinea Pigs; D006220:Haloperidol / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010423:Pentazocine / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D017480:Receptors, sigma
D014150:Antipsychotic Agents; D002227:Carbazoles; D015259:Dopamine Agents; D006146:Guanidines; D010880:Piperidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C026539:preclamol; C034931:rimcazole; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine