Multiple [3H]DTG binding sites in guinea pig cerebellum: evidence for the presence of non-specific binding.
The characteristics of the low affinity component of 1,3-di(2-[5-3H]tolyl)guanidine binding to the guinea pig cerebellum were investigated. Saturation binding assays where sigma 1 receptors were masked with dextrallorphan indicated that 1,3-di(2-[5-3H]tolyl)guanidine bound to cerebellar membranes in a fashion best described by a 1 site+non-specific binding model with a low density of specific binding sites (Bmax approximately 200 fmol/mg protein). Boiling the cerebellar membranes before addition to the saturation assay had no effect on the density of 1,3-di(2-[5-3H]tolyl)guanidine binding. In contrast, both the Kd and Bmax for 1,3-di(2-[5-3H]tolyl)guanidine binding to liver membranes was significantly reduced by boiling, as was the density of [3H](+)-pentazocine binding to cerebellum and liver. Thus, a substantial component of 1,3-di(2-[5-3H]tolyl)guanidine binding in the guinea pig cerebellum is to non-specific, proteinaceous binding sites with some of the pharmacological characteristics of the sigma 2 binding site.
Basile
A S
AS
Laboratory of Neuroscience, NIDDK, NIH, Bethesda, MD 20892.
DeCosta
B
B
Paul
I A
IA
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism* / Q000493:pharmacokinetics; D001667:Binding, Competitive / Q000187:drug effects; D002531:Cerebellum / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism* / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007977:Levallorphan / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D010423:Pentazocine / Q000494:pharmacology; D017480:Receptors, sigma / Q000378:metabolism
D000927:Anticonvulsants; D006146:Guanidines; D017480:Receptors, sigma; D007977:Levallorphan; C044130:dextrallorphan; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine