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

Paul M. Colombani, Adelaide Robb, Allan D. Hess

Research output: Contribution to journalArticle

Abstract

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 cyclospotin 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.

Original languageEnglish (US)
Pages (from-to)337-339
Number of pages3
JournalScience
Volume228
Issue number4697
DOIs
StatePublished - Jan 1 1985

ASJC Scopus subject areas

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