Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes rat aorta via nitric oxide formation.
Thapsigargin induced endothelium-dependent relaxation and cGMP production in rat thoracic aorta, and these effects were inhibited by nitric oxide (NO) pathway inhibitors, a calmodulin inhibitor and removal of Ca2+, suggesting that NO is involved in the thapsigargin-induced relaxation. Thapsigargin may deplete Ca2+ stores in the endothelial cells by inhibiting the Ca(2+)-ATPase, a Ca2+ pump, which in turn triggers influx of extracellular Ca2+, leading to activation of constitutive NO synthase and resultant NO generation. The NO thus formed may activate soluble guanylate cyclase to produce cGMP in the vascular smooth muscle.
Moritoki
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Hisayama
T
T
Kondoh
W
W
Takeuchi
S
S
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D006152:Cyclic GMP / Q000096:biosynthesis; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D013189:SRS-A / Q000037:antagonists & inhibitors; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D000634:Aminoquinolines; D013189:SRS-A; D013729:Terpenes; D019335:Nitroarginine; D009569:Nitric Oxide; D019284:Thapsigargin; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D000252:Calcium-Transporting ATPases; D006152:Cyclic GMP; D002118:Calcium