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Angiotensin II‐activated Ca 2+ entry‐induced release of Ca 2+ from intracellular stores in rat portal vein myocytes
Author(s) -
Morel J.L.,
MacrezLeprêtre N.,
Mironneau J.
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.tb15368.x
Subject(s) - ryanodine receptor , angiotensin ii , intracellular , losartan , endocrinology , chemistry , medicine , biophysics , patch clamp , receptor , biology , biochemistry
1 . The action of angiotensin II (AII) was studied in single myocytes from rat portal vein in which the cytoplasmic Ca 2+ concentration was estimated by emission from dyes Fura‐2 or Indo‐1 and the Ca 2+ channel current was measured with the whole‐cell mode of the patch‐clamp technique. 2 . Most of the AII‐evoked increases in [Ca 2+ ] i were reduced by about 60% after pretreatment with ryanodine and caffeine to deplete intracellular Ca 2+ stores. However, in some cells the AII‐induced Ca 2+ responses were of small amplitude and resembled those obtained in the presence of ryanodine and caffeine. Both types of Ca 2+ responses induced by AII were selectively inhibited by losartan, suggesting that the AII effects resulted from activation of the angiotensin AT 1 receptors. 3 . The concentration‐response curve to AII had an EC 50 value close to 1 nM for the increase in [Ca 2+ ] i obtained after depletion of intracellular Ca 2+ stores. This value was increased to around 18 nM in experiments where the intracellular Ca 2+ stores were not depleted. 4 . AII‐evoked Ca 2+ responses were abolished in the absence of external Ca 2+ and in the presence of 1 μ m oxodipine to block L‐type Ca 2+ channels. 5 . Intracellular applications of the InsP 3 receptor antagonist, heparin or an anti‐PdtIns antibody did not modify AII‐induced Ca 2+ responses. 6 . Our results show that AII releases Ca 2+ from intracellular stores without involving InsP 3 but through a Ca 2+ release mechanism activated by Ca 2+ influx through L‐type Ca 2+ channels.