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Science 19 April 1985:
Vol. 228. no. 4697, pp. 337 - 339
DOI: 10.1126/science.3885394
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Articles

Science, Vol 228, Issue 4697, 337-339
Copyright © 1985 by American Association for the Advancement of Science

articles

Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes

PM Colombani, A Robb, and AD Hess

Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response.


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