Tetrandrine inhibits Ca2+ release-activated Ca2+ channels in vascular endothelial cells.
The effects of tetrandrine (TET), a Ca2+ antagonist of bis-benzylisoquinoline alkaloid origin, on cultured single bovine pulmonary artery endothelial cells were examined using fluorescence ratio imaging and whole-cell attached patch-clamp techniques. Thapsigargin (TSG, 100 nM), a selective endoplasmic reticulum Ca2+-ATPase pump inhibitor known to induce the release of nitric oxide (NO) from vascular endothelial cells via a Ca2+-dependent manner, caused a rapid elevation of cytosolic Ca2+ concentration, which was inhibited by 30 microM TET. In whole-cell patch-clamp study using the same vascular endothelial cells, addition of 100 nM TSG caused a significant enhancement of depolarization-evoked Ca2+-dependent, outward K+ currents, which could also be abolished by 30 microM TET. The present results demonstrate directly that TET, in addition to its known inhibitory effects on vascular smooth muscle by virtue of its Ca2+ antagonistic actions, also inhibits NO production by the endothelial cells through blockade of Ca2+ release-activated Ca2+ channels.
Kwan
C Y
CY
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. kwancy@fhs.mcmaster.ca
Leung
Y M
YM
Kwan
T K
TK
Daniel
E E
EE
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C009438:tetrandrine; D000252:Calcium-Transporting ATPases; D002118:Calcium