HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Misra, U. K. Articles by Pizzo, S. V. Search for Related Content PubMed PubMed Citation Articles by Misra, U. K. Articles by Pizzo, S. V.

Cyclosporin A Inhibits Inositol 1,4,5-Trisphosphate Binding to Its Receptors and Release of Calcium from Intracellular Stores in Peritoneal Macrophages¹

Department of Pathology, Duke University Medical Center, Durham, NC 27710

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 ₂-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.

This article has been cited by other articles:

				L. Mondin, H. Balghi, B. Constantin, C. Cognard, and S. Sebille Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells death Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1133 - C1145. [Abstract] [Full Text] [PDF]

				O. B. Balemba, A. C. Bartoo, M. T. Nelson, and G. M. Mawe Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G467 - G476. [Abstract] [Full Text] [PDF]

				V. Calderaro, M. Boccellino, G. Cirillo, L. Quagliuolo, D. Cirillo, and A. Giovane Cyclosporine A Amplifies Ca2+ Signaling Pathway in LLC-PK1 Cells through the Inhibition of Plasma Membrane Ca2+ Pump J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1435 - 1442. [Abstract] [Full Text] [PDF]

				P. D. Arora, L. Silvestri, B. Ganss, J. Sodek, and C. A. G. McCulloch Mechanism of Cyclosporin-induced Inhibition of Intracellular Collagen Degradation J. Biol. Chem., April 20, 2001; 276(17): 14100 - 14109. [Abstract] [Full Text] [PDF]