MONOCLONAL ANTIIDIOTYPIC ANTIBODY TO A POTENT THROMBOXANE-A2 RECEPTOR ANTAGONIST AND ITS INTERACTION WITH THROMBOXANE-A2 RECEPTOR

被引:0
作者
KAN, WM [1 ]
TAI, HH [1 ]
机构
[1] UNIV KENTUCKY,COLL PHARM,DIV MED CHEM & PHARMACEUT,LEXINGTON,KY 40536
关键词
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A monoclonal anti-idiotypic antibody that interacts with thromboxane A2 receptor was generated using an anti-idiotypic approach. Idiotypic antibodies against a potent receptor antagonist, HS-145, were generated in rabbit. The idiotypic antibodies were then selected by an affinity procedure using SQ29,548-Affi-Gel-102 matrix. The selected idiotypic antibodies were used as surrogate receptor for anti-idiotypic antibody generation. A mouse monoclonal antibody, 3D-9E-12, was generated. It was shown to displace I-125-HS-145 from affinity-purified idiotypic antibodies. It also inhibits I-125-IS-145 binding to thromboxane A2 receptor in human platelet membranes in a dose-dependent manner. Furthermore, it attenuated U46,619-induced increase in [S-35]guanosine 5'-O-(thiotriphosphate) binding and GTPase activity in human platelet membranes. Finally, it inhibited U46,619- but not PAF-induced platelet aggregation. These results indicate that 3D-9E-12 acts as a specific antagonist in the thromboxane A2 receptor.
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页码:6364 / 6370
页数:7
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