[3H]GBR 12935 binding in platelets: a possible association with cytochrome P-450IID6?

The nature of [3H] (1-[2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) (GBR 12935) binding to human platelets was investigated. A common property of the inhibitors of this binding was their association with the cytochrome P-450 system. cis-Flupenthixol and (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl) piperazine dihydrochloride) (GBR 12909) biphasically inhibited the binding. The fraction of [3H]GBR 12935 binding that was inhibited by low concentrations of cis-flupenthixol was sensitive to protease treatment. [3H]GBR 12935 binding in this fraction was saturable and of high affinity (Kd 4.5 nM). The present results reveal that [3H]GBR 12935 binds to multiple sites in platelets and suggest that part of the binding is associated with cytochrome P-450IID6.