Calmodulin antagonists bind to sodium‐dependent high‐affinty binding sites for tritiated imipramine

Abstract

AbstractEffects of calmodulin antagonists on the binding of tritiated imipramine and inhibition of serotonin uptake were tested in brain and platelet preparations. Naphthalene sulfonamidetype calmodulin antagonists generally inhibited specific [3H]‐Imipramine binding (as well as serotonin uptake) with affinities greater than or equal to those reported for binding to calmodulin itself. The binding inhibition did not require the presence of calcium and was not affected by ethylenediaminetetraacetic acid. Other calmodulin antagonists which do not have naphthalene sulfonamide structures did not inhibit [3H]‐Imipramine binding. These results raise the possibility that the structural similarity between imipramine and the naphthalene sulfonamide cerivatives may be sufficient to allow direct competition at the binding site for [3H]‐Imipramine. This is of great importance for calmodulin biochemistry since at these concentrations, the inhibitors were previously thought to interact virtually exclusively with calmodulin. © 1992 Wiley‐Liss, Inc.