Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes.
Science
; 228(4697): 337-9, 1985 Apr 19.
Article
em En
| MEDLINE
| ID: mdl-3885394
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calmodulina
/
Linfócitos T
/
Ciclosporinas
Idioma:
En
Ano de publicação:
1985
Tipo de documento:
Article