PLANT ALKALOIDS, TETRANDRINE AND HERNANDEZINE, INHIBIT CALCIUM-DEPLETION STIMULATED CALCIUM-ENTRY IN HUMAN AND BOVINE ENDOTHELIAL-CELLS

Depletion of internal Ca2+ stores causes capacitative Ca2+ entry which occurs through non-selective cation channels sensitive to blockade by SK&F 96365. Recently, alkaloids of Chinese herbal medicinal origin, t etrandrine and hernandezine, have been shown to possess actions includ ing inhibition of Ca2+ channels in non-excitable cell types. In this s tudy, we compared the actions of these novel inhibitors to those of SK &F 96365 in fura-2-loaded endothelial cells from human umbilical vein and bovine pulmonary artery. Depletion of Ca2+ from the internal store s was accomplished in Ca2+-free medium using an endoplasmic reticulum Ca2+ pump inhibitor, cyclopiazonic acid (CPA) or receptor agonists, hi stamine and bradykinin. Stimulation with histamine or bradykinin cause d a marked and rapid transient increase in Ca2+ signal whereas CPA cau sed a smaller amplitude increase of longer duration. Restoring Ca2+ to the medium caused marked and sustained increases in the fluorescence indicating movement of Ca2+ into the cytosol presumably stimulated by the emptied Ca2+ stores. SK&F 96365 as well as tetrandrine and hemande zine antagonized depletion-induced Ca2+ entry. The results suggest tha t these putative inhibitors interact with Ca2+ entry triggered by depl etion of the internal Ca2+ stores and their action is presumed to be o n the non-selective cation channels. Their effectiveness may be enhanc ed by the mechanisms which lead to the opening of the Ca2+ influx chan nel.