Inhibition by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin inhibitor, of dopamine release from...

The release of preloaded [(3)H]dopamine by the synaptosomal fraction prepared from rat forebrain was examined in the presence and absence of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor. The release induced by high K(+) was blocked by W-7 in a concentration-dependent manner after the pretreatment with and in the presence of the inhibitor. The inhibition by W-7 may specifically involve calmodulin, because little effects were seen with N-(6-aminohexyl)-naphthalenesulfonamide, an analog of W-7 with only a low affinity for calmodulin. W-7 may not affect the voltage-dependent Ca(2+) channel of synaptosomal plasmalemma, since the inhibitor produced no change in the synaptosomal (45)Ca(2+) uptake induced by high K(+) depolarization. Thus, calmodulin may play a role in transmitter release and may function at the step(s) after the increase of free Ca(2+) concentration in the cytosol of the nerve terminal. W-7 affected only to a small extent [(3)H]dopamine release in the presence of A23187 plus Ca(2+).