Modulation of adhesion-dependent cAMP signaling by echistatin and alendronate.

We 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.
AuthorsJ H Fong, D E Ingber
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 221 Issue 1 Pg. 19-24 (Apr 5 1996) ISSN: 0006-291X [Print] UNITED STATES
PMID8660334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Diphosphonates
  • Oligopeptides
  • Peptides
  • echistatin
  • arginyl-glycyl-aspartic acid
  • Cyclic AMP
  • Alendronate
  • Alendronate
  • Binding Sites
  • Cell Adhesion
  • Cyclic AMP (metabolism)
  • Diphosphonates (pharmacology)
  • Endothelium, Vascular (cytology, drug effects, metabolism)
  • Extracellular Matrix (metabolism)
  • Humans
  • Oligopeptides (metabolism)
  • Peptides (pharmacology)
  • Signal Transduction (drug effects)

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