Verapamil inhibits serotonin uptake of endothelial cells in culture by a mechanism unrelated to Ca2+ channel blockade

Abstract

Verapamil inhibited Na⁺‐dependent uptake of serotonin (5‐HT) by bovine pulmonary artery endothelial cells in culture both exposed to room air and stimulated by prior exposure to anoxia. The effect of verapamil occurred even in the absence of Ca²⁺ from the assay medium. Although absence of Ca²⁺ from the medium moderately reduced 5‐HT uptake, stimulation of uptake was nevertheless observed for cells previously exposed to anoxia. Verapamil altered the Km, but not the Vmax, of 5‐HT uptake. There was no change in ⁴⁵Ca²⁺ uptake or release by cells previously exposed to anoxia as compared to those exposed to room air and verapamil did not influence ⁴⁵Ca²⁺ fluxes by either set of cells. It is concluded that verapamil inhibits 5‐HT uptake by endothelial cells through a mechanism other than Ca²⁺ channel blockade; the results are consistent with competitive inhibition of a 5‐HT carrier. The stimulatory effect of anoxia on 5‐HT uptake does not occur through a change in Ca²⁺ fluxes.