TY - JOUR
T1 - Deaggregation of human platelets in vitro by an RGD analog antagonist of platelet glycoprotein IIb/IIIa receptors
AU - Haskel, Ethan J.
AU - Abendschein, Dana R.
N1 - Funding Information:
We thank Paul Myer, D.V.M. for technical assistance, Kelly Hall for typing the manuscript, and Monsanto/Searle for providing RGDY and RGEY. This work was supported in part by NHLBI SCOR in Ischemic Heart Disease HL 17646. Dr. Haskel is a Fellow of the American Heart Association, Missouri Affiliate.
PY - 1989/12/15
Y1 - 1989/12/15
N2 - Binding of fibrinogen to platelet glycoprotein (GP) IIb/IIIa receptors is essential for normal platelet aggregation. We investigated whether inhibition of GP IIb/IIIa receptors with arginine-glycine-aspartate-O-methyltyrosine amide (RGDY), an analog of the receptor recognition sequence found in fibrinogen, is associated with platelet deaggregation. Platelets from five healthy human subjects that were maximally aggregated by addition of adenosine diphosphate to platelet-rich plasma were deaggregated in a dose-dependent manner by subsequent addition of RGDY (86.5 ± 6.2%, 68.2 ± 4.3%, 44.9 ± 6.4%, and 31.6 ± 4.1% for RGDY concentrations of 400, 200, 133, and 67 μM, respectively vs. 7.8 ± 2.9% for saline control samples, p < 0.0001). The extent of deaggregation was decreased as the time of addition of RGDY (400 μM) after maximal aggregation increased (85.6 ± 6.7%, 58.5 ± 12.6%, 47.1 ± 2.7%, and 37.1 ± 4.2% for 0, 1, 3, and 5 minute intervals, respectively, vs. 8.3 ± 3.1% in control samples, n = 4, p < 0.0001) consistent with the occurrence of irreversible aggregation. Thus, RGDY can rapidly and extensively deaggregate human platelets under certain conditions which may enhance its antithrombotic efficacy.
AB - Binding of fibrinogen to platelet glycoprotein (GP) IIb/IIIa receptors is essential for normal platelet aggregation. We investigated whether inhibition of GP IIb/IIIa receptors with arginine-glycine-aspartate-O-methyltyrosine amide (RGDY), an analog of the receptor recognition sequence found in fibrinogen, is associated with platelet deaggregation. Platelets from five healthy human subjects that were maximally aggregated by addition of adenosine diphosphate to platelet-rich plasma were deaggregated in a dose-dependent manner by subsequent addition of RGDY (86.5 ± 6.2%, 68.2 ± 4.3%, 44.9 ± 6.4%, and 31.6 ± 4.1% for RGDY concentrations of 400, 200, 133, and 67 μM, respectively vs. 7.8 ± 2.9% for saline control samples, p < 0.0001). The extent of deaggregation was decreased as the time of addition of RGDY (400 μM) after maximal aggregation increased (85.6 ± 6.7%, 58.5 ± 12.6%, 47.1 ± 2.7%, and 37.1 ± 4.2% for 0, 1, 3, and 5 minute intervals, respectively, vs. 8.3 ± 3.1% in control samples, n = 4, p < 0.0001) consistent with the occurrence of irreversible aggregation. Thus, RGDY can rapidly and extensively deaggregate human platelets under certain conditions which may enhance its antithrombotic efficacy.
KW - blood platelets
KW - platelet antagonists
KW - platelet membrane glycoprotein complex IIb/IIIa
UR - http://www.scopus.com/inward/record.url?scp=0024803733&partnerID=8YFLogxK
U2 - 10.1016/0049-3848(89)90286-7
DO - 10.1016/0049-3848(89)90286-7
M3 - Article
C2 - 2633401
AN - SCOPUS:0024803733
SN - 0049-3848
VL - 56
SP - 687
EP - 695
JO - Thrombosis Research
JF - Thrombosis Research
IS - 6
ER -