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An Arg-Gly-Asp peptide stimulates Ca2+ efflux from osteoclast precursors through a novel mechanismWe examined the effect of a peptide containing the Arg-Gly-Asp (RGD) sequence on 45Ca2+ efflux from osteoclast precursors. 45Ca(2+)-loaded osteoclast precursors were treated with GRGDSP (170 microM) for 10 min after 30 min of basal perfusion with a bicarbonate-containing buffer. GRGDSP significantly increased fractional efflux of Ca2+ from treated cells compared with vehicle-treated cells (P < 0.01) or cells treated with up to 200 micrograms/ml of a control peptide containing GRGESP. The effect of RGD was sustained for 15 min after the peptide was removed from the perfusate, but control levels of Ca2+ efflux returned by 1 h. The Ca2+ efflux effect of GRGDSP was most likely due to activation of the plasma membrane Ca(2+)-adenosinetriphosphatase (Ca(2+)-ATPase) pump, as indicated by its inhibition with vanadate and a calmodulin antagonist, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, and the absence of an effect of Na+/Ca2+ exchange inhibition. An inhibitor of cyclic nucleotide-dependent protein kinases, N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (0.1 mM), failed to inhibit GRGDSP-stimulated Ca2+ efflux. However, genistein and herbimycin A, inhibitors of protein-tyrosine kinases, blocked Ca2+ efflux stimulated by GRGDSP. The results indicate that RGD sequences of matrix proteins may stimulate Ca2+ efflux from osteoclasts through activation of protein-tyrosine kinases and suggest that GRGDSP-stimulated Ca2+ efflux is mediated via the plasma membrane Ca(2+)-ATPase.
Document ID
20050000365
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Yamakawa, K.
(Jewish Hospital, Washington University Medical Center St. Louis, Missouri 63110)
Duncan, R.
Hruska, K. A.
Date Acquired
August 22, 2013
Publication Date
April 1, 1994
Publication Information
Publication: The American journal of physiology
Volume: 266
Issue: 4 Pt 2
ISSN: 0002-9513
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: AR-41677
CONTRACT_GRANT: AR-39561
CONTRACT_GRANT: DK-09976
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Musculoskeletal
Non-NASA Center

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