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Modulation of adhesion-dependent cAMP signaling by echistatin and alendronateWe measured intracellular cAMP levels in cells during attachment and spreading on different extracellular matrix (ECM) proteins. Increases in cAMP were observed within minutes when cells attached to fibronectin, vitronectin, and a synthetic RGD-containing fibronectin peptide (Petite 2000), but not when they adhered to another integrin alpha nu beta 3 ligand, echistatin. Because echistatin also inhibits bone resorption, we measured the effects of adding another osteoporosis inhibitor, alendronate, in this system. Alendronate inhibited the cAMP increase induced by ligands that primarily utilize integrin alpha nu beta 3 (vitronectin, Peptite 2000), but not by fibronectin which can also use integrin alpha 5 beta 1. These results show that cell adhesion to ECM can increase intracellular cAPM levels and raise the possibility that inhibitors of osteoporosis may act, in part, by preventing activation of this pathway by integrins.
Document ID
20040173235
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Fong, J. H. (Children's Hospital & Harvard Medical School Boston, Massachusetts 02115, United States)
Ingber, D. E.
Date Acquired
August 22, 2013
Publication Date
April 5, 1996
Publication Information
Publication: Biochemical and biophysical research communications
Volume: 221
Issue: 1
ISSN: 0006-291X
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Number 40-20
NASA Discipline Cell Biology
NASA Program Space Biology
Non-NASA Center