Abstract:
:We studied the effect of glycoprotein GPIIb/IIIa (integrin alpha IIb beta 3) receptor occupancy by adenosine 5',1-thiotriphosphate (ATP alpha S), a competitive inhibitor of the ADP receptor, by fibrinogen, and by peptides containing the RGD (Arg-Gly-Asp) sequence as RGDW (Arg-Gly-Asp-Trp), RGDS (Arg-Gly-Asp-Ser), or the negative control RGGW (Arg-Gly-Gly-Trp) on human platelet physiological functions: aggregation, ATP secretion, and [Ca2+]in. As the presence of a nucleotide binding site on GPIIb alpha has been demonstrated in platelets [N. J. Greco, N. Yamamoto, B. W. Jackson, N. N. Tandon, M. Moos, and G. A. Jamieson (1991) J. Biol. Chem. 266, 13627-13633], we studied the effect of ATP alpha S, which specifically binds to this site, on platelet activation. We observed that ATP alpha S inhibited aggregation by thrombin, ADP, PMA, and ionophore A23187. Moreover, ATP alpha S dose dependently inhibited ATP secretion by ionophore A23187 and Ca2+ transients by thrombin and vasopressin in both the presence and absence of external Ca2+. Fibrinogen, although induced by a potentiation of platelet aggregation, inhibited ATP secretion and [Ca2+]in elevation induced by low thrombin concentrations or by vasopressin, interfering with both Ca2+ entry and Ca2+ release by the intracellular stores. RGD peptides, which specifically bind to GPIIb/IIIa, inhibited aggregation, secretion, and Ca2+ transients by thrombin, whereas the negative control RGGW did not exert any effect. We conclude that the occupancy of the GPIIb/IIIa receptor binding sites modulates platelet function by giving an inhibitory outside-in signal in platelets, particularly effective in platelets stimulated with low agonist doses. We suggest that ATP alpha S, fibrinogen, or RGD compounds, by interacting with GPIIb/IIIa receptor, prime some intracellular negative feedback mechanisms, which prevent further activation of circulating platelets by low-intensity stimuli and intravascular aggregation.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Padoin E,Alexandre A,Cavallini L,Polverino de Laureto P,Rao GH,Doni MGdoi
10.1006/abbi.1996.0408subject
Has Abstractpub_date
1996-09-15 00:00:00pages
407-13issue
2eissn
0003-9861issn
1096-0384pii
S0003986196904087journal_volume
333pub_type
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pub_type: 杂志文章
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journal_title:Archives of biochemistry and biophysics
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更新日期:1994-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-08-15 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1006/abbi.1999.1463
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pub_type: 杂志文章
doi:10.1006/abbi.2001.2662
更新日期:2002-01-15 00:00:00
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pub_type: 杂志文章
doi:10.1016/0003-9861(91)90011-7
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更新日期:2004-12-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:1987-11-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.2000.1794
更新日期:2000-05-15 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:2008-01-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1998.0847
更新日期:1998-09-15 00:00:00