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Inhibition by SK&F96365 of NO‐mediated relaxation induced by Ca 2+ ‐ATPase inhibitors in rat thoracic aorta
Author(s) -
Moritoki Hideki,
Hisayama Tetsuhiro,
Takeuchi Shougo,
Kondoh Wataru,
Inoue Shinnichi,
Kida Kan
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15319.x
Subject(s) - cyclopiazonic acid , thapsigargin , chemistry , biophysics , acetylcholine , nifedipine , channel blocker , atpase , endocrinology , medicine , calcium , biochemistry , endoplasmic reticulum , biology , enzyme , organic chemistry
1 We investigated the effect of SK&F96365, a putative inhibitor of receptor‐operated Ca 2+ entry, on the endothelium‐dependent, NO‐mediated relaxation and cyclic GMP formation induced by Ca 2+ ‐ATPase inhibitors in rat thoracic aorta. 2 SK&F96365 inhibited cyclopiazonic acid or thapsigargin‐induced relaxation and cyclic GMP formation mediated by a constitutive NO synthase, which is known to be activated by the Ca 2+ that enters into the endothelial cells via plasma membrane Ca 2+ channels subsequent to depletion of stored Ca 2+ by Ca 2+ ‐ATPase inhibitors. 3 SK&F96365 also inhibited relaxation and cyclic GMP formation induced by acetylcholine, without affecting those induced by nitroprusside and A23187. 4 Ni 2+ attenuated relaxation and cyclic GMP formation induced by cyclopiazonic acid and acetylcholine. 5 In contrast, the voltage‐dependent Ca 2+ channel blocker, nifedipine, did not affect the relaxation caused by Ca 2+ ‐ATPase inhibitors. 6 These results suggest that endothelium‐dependent, NO‐mediated relaxation of the arteries induced by Ca 2+ ‐ATPase inhibitors is triggered by the Ca 2+ that enters into endothelial cells via receptor‐operated channels (SK&F96365‐sensitive channels) subsequent to depletion of stored Ca 2+ as a result of inhibition of the Ca 2+ ‐ATPase (Ca 2+ pump) of the stores.