Verapamil inhibits serotonin uptake of endothelial cells in culture by a mechanism unrelated to Ca2+ channel blockade.
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.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism*; D007700:Kinetics; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D012701:Serotonin; D012964:Sodium; D014700:Verapamil; D002118:Calcium