Cyclosporin A inhibits inositol 1,4,5-trisphosphate binding to its receptors and release of calcium from intracellular stores in peritoneal macrophages.

Published

Journal Article

We have studied the effects of the immunosuppressive drug cyclosporin A (CsA) on the generation of inositol 1,4,5-trisphosphate (IP3) and intracellular Ca2+ levels elicited upon ligation of murine macrophage receptors for alpha2-macroglobulin, bradykinin, epidermal growth factor, and platelet-derived growth factor. Preincubation of cells with CsA (500 ng/ml), either alone or with the various ligands, did not inhibit the synthesis of IP3. However, we observed 70-80% inhibition of the binding of [3H]IP3 to IP3 receptors on macrophage membranes isolated from CsA-treated macrophages. Preincubation of macrophages with CsA abolished IP3-mediated release of Ca2+ from intracellular stores and Ca2+ entry from the extracellular medium observed when macrophage receptors were stimulated with ligands in the absence of CsA. Preincubation of macrophages with CsA also significantly inhibited DNA synthesis induced by ligands for all four receptors studied. Thus in macrophages, as in T cells, CsA blocks receptor-activated signal transmission pathways characterized by an initial increase in intracellular Ca2+ concentration. This inhibition appears to result from a drug effect on IP3 receptors.

Full Text

Duke Authors

Cited Authors

  • Misra, UK; Gawdi, G; Pizzo, SV

Published Date

  • December 1998

Published In

Volume / Issue

  • 161 / 11

Start / End Page

  • 6122 - 6127

PubMed ID

  • 9834096

Pubmed Central ID

  • 9834096

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Language

  • eng