KINASE INHIBITORS COMPETE WITH IMIPRAMINE FOR BINDING AND INHIBITION OF SEROTONIN TRANSPORT

Effects of kinase inhibitors and activators on the binding of tritiated imipramine and inhibition of serotonin uptake were tested in platelets. The majority of compounds inhibited specific [H-3]imipramine binding and serotonin uptake with affinities similar to those reported for their action on protein kinases themselves. Many of these compounds are derivatives with modified naphthalenesulfonamide or isoquinolinesulfonamide structures, which appear to compete directly with imipramine for binding to the serotonin transporter. This is of great importance for studies involving kinase regulation since at these concentrations, the inhibitors and activators were previously thought to interact virtually exclusively with protein kinases.