Thapsigargin induces an endothelium-dependent, intracellular calcium ion-dependent vasodilation in vitro.
The effect of thapsigargin, a specific inhibitor of intracellular Ca(2+)-ATPases, on endothelium-dependent relaxation was studied in the guinea pig thoracic aorta. Thapsigargin (1 nM-1 microM) produced a concentration-dependent relaxation of aortic strips precontracted by phenylephrine (0.1 microM) in the presence and absence of extracellular Ca2+. Thapsigargin (0.1 microM-10 microM) produced the concentration-dependent contraction in aortic strips with no endothelium in the presence and absence of extracellular Ca2+. The relaxant effect of thapsigargin (1 microM) was not attained in a de-endothelialised aortic strip. NG-nitro-L-arginine (10 nM-0.1 mM), a blocker of NO synthase, produced a concentration-dependent inhibition of thapsigargin-induced relaxation. Thapsigargin failed to produce vasodilation by pretreatment of aortic strips with NG-nitro-L-arginine (10 microM). Thapsigargin (1 microM) increased tissue levels of guanosine 3', 5' cyclic-monophosphate in aortic strips preincubated with phenylephrine (0.1 microM). The results suggest that the intracellular Ca2+ mobilization in endothelial cells by thapsigargin is of significance in the endothelium-dependent relaxation of guinea pig thoracic aorta.
Department of Pharmacology, Kobe University School of Medicine, Japan.
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Matsuyama
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Shuntoh
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Katayama
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Tanaka
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D002273:Carcinogens; D013729:Terpenes; D019335:Nitroarginine; D009569:Nitric Oxide; D019284:Thapsigargin; D001120:Arginine; D006152:Cyclic GMP; D002118:Calcium