Inhibition of serotonin uptake into mouse brain synaptosomes by ionophores and ion-channel agents

[ 3H]Serotonin uptake into mouse cerebrocortical synaptosomes was decreased by the K + ionophore valinomycin, the K + and Na + ionophore gramicidin, and the proton ionophore carbonylcyanidem-chlorophenylhydrazone. The Na +/H + exchanger monensin reduced uptake at non-depolarizing concentrations. Uptake was also decreased by inhibition of the Na +,K +-ATPase with ouabain and by tetrodotoxin-sensitive activation of voltage-dependent sodium channels with veratridine, batrachotoxin and scorpion venom. In contrast, the Ca 2+ channel agents BAY K8644 and nimodipine were ineffective. The effect of reducing the Na + gradient depended upon whether the internal Na + concentration was raised (i.e. by scorpion venom, monensim) or the external Na + concentration was lowered (37 mM NaCl in the medium).