Endothelin-induced prostacyclin production in rat aortic endothelial cells: role of calcium.
Endothelin (ET) is a potent vasoconstrictor peptide, released from endothelial cells, which is associated with prostaglandin (PG) release. The mechanism by which ET causes the release of PG is not clearly understood. We used rat aortic endothelial cells to investigate the role of calcium (Ca2+) in ET-1-induced prostacyclin (PGI2) release. ET-1 (10(-9) M) produced a significant increase in PGI2 release. Pretreatment of rat aortic endothelial cells with different doses (10(-9) M and 10(-6) M) of diltiazem (voltage-sensitive L-type calcium channel blocker) produced significant inhibition of ET-1- and PDBu-induced PGI2 release. Inhibition was first noted at 10(-9) M and was complete at 10(-6) M. Conversely, pretreatment of rat aortic endothelial cells with different doses (10(-9) M and 10(-6) M) of calcium channel blockers (thapsigargin, an intracellular calcium channel blocker or conotoxin, a voltage-sensitive N-type calcium channel blocker) produced no changes on ET-1- or PDBu-induced PGI2 release. These results provide further support for the concept that PKC mediates ET-induced PGI2 release in rat aortic endothelial cells via an increase in intracellular calcium and this increase is due to the influx of extracellular calcium and not to the release of calcium from the sarcoplasmic reticulum.
Oriji
G K
GK
Department of Biology, College of Science and Health, William Paterson University, Wayne, NJ 07470, USA.
D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D019284:Thapsigargin / Q000008:administration & dosage / Q000494:pharmacology
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D015240:Phorbol 12,13-Dibutyrate; D019284:Thapsigargin; D011464:Epoprostenol; D004110:Diltiazem; D002118:Calcium