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Cyclosporin A increases basal intracellular calcium and calcium responses to endothelin and vasopressin in human coronary myocytes
Author(s) -
Frapier Jean Marc,
Choby Cécile,
Mangoni Matteo E.,
Nargeot Joël,
Albat Bernard,
Richard Sylvain
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02269-4
Subject(s) - endocrinology , medicine , vasoconstriction , endothelin receptor , vasopressin , calcium , basal (medicine) , agonist , calcium in biology , chemistry , myocyte , endothelin 1 , stimulation , intracellular , fura 2 , receptor , pharmacology , biochemistry , insulin , enzyme , cytosol
Cyclosporin A (CsA) is a widely used immunosuppressive agent with severe side effects including hypertension. Here, we investigated the effects of CsA on intracellular free calcium ([Ca 2+ ] i ) and the mechanisms involved in vasoconstriction in cultured human coronary myocytes. We used the Fura‐2 technique for Ca 2+ imaging. Acute application of CsA at therapeutic concentrations (0.1–10 μmol/l) had no effect. Chronic exposure to CsA (1 μmol/l) for 24 h induced a small (20 nmol/l) but highly significant increase of basal [Ca 2+ ] i and enhanced the occurrence of spontaneous Ca 2+ oscillations. Endothelin‐ and vasopressin‐induced rises of [Ca 2+ ] i were also enhanced. The demonstration that CsA increases basal [Ca 2+ ] i in addition to its impact on agonist receptor stimulation is of major importance for new therapeutic approaches.