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Titolo:
Comparative specificity of platelet alpha(IIb)beta(3) integrin antagonists
Autore:
Thibault, G; Tardif, P; Lapalme, G;
Indirizzi:
Inst Rech Clin Montreal, Lab Biol Cellulaire Hypertens, Montreal, PQ H2W 1R7, Canada Inst Rech Clin Montreal Montreal PQ Canada H2W 1R7 al, PQ H2W 1R7, Canada Univ Montreal, Montreal, PQ, Canada Univ Montreal Montreal PQ CanadaUniv Montreal, Montreal, PQ, Canada
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 296, anno: 2001,
pagine: 690 - 696
SICI:
0022-3565(200103)296:3<690:CSOPAI>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBRINOGEN RECEPTOR ANTAGONISTS; GLYCOPROTEIN IIB/IIIA INHIBITORS; IIB-IIIA; ANTITHROMBOTIC EFFICACY; ANTIPLATELET EFFICACY; NEOINTIMA FORMATION; ALPHA(V)BETA(3); AGGREGATION; POTENT; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Thibault, G Inst Rech Clin Montreal, Lab Biol Cellulaire Hypertens, 110 Ave Pins Ouest, Montreal, PQ H2W 1R7, Canada Inst Rech Clin Montreal 110 Ave Pins Ouest Montreal PQ Canada H2W 1R7
Citazione:
G. Thibault et al., "Comparative specificity of platelet alpha(IIb)beta(3) integrin antagonists", J PHARM EXP, 296(3), 2001, pp. 690-696

Abstract

Several platelet alpha (IIb)beta (3) integrin antagonists have been designed as preventive agents against the formation of arterial thrombi. Althoughthe potency of these compounds in inhibiting platelet aggregation is in the nanomolar range, their specificity on other integrins that can bind ligands through an arginine-glycine-aspartic acid (RGD) motif is far from being well established. For instance, some cyclic RGD peptides can also interact with alpha (v)beta (3) integrin. We used a novel pharmacological assay, based on SDS-stable interaction between I-125-echistatin and RGD-dependent integrins, to evaluate the specificity of several RGD compounds on integrins present on rat cardiac fibroblasts and human skin fibroblasts. None of the RGD peptidomimetics tested (L-734,217, lamifiban, Ro 44-3888, SR 121566A, BIBU-52, XV459) could interact with either alpha (v)beta (3) and alpha (8)beta (1) on rat fibroblasts or with alpha (v)beta (3) and alpha (v)beta (1) onhuman fibroblasts. Cyclic RGD peptides showed some potency (3-80 muM) on rat and human integrins with an alpha (v) subunit. We also compared the potency of these compounds on platelets. All RGD compounds demonstrated IC50 between 0.6 and 530 nM on basal human platelets. Activation of the receptor with thrombin resulted in a 2- to 60-fold increase in potency, with L-734,217 and BIBU-52 showing the largest difference. On basal and thrombin-activated rat platelets, only eptifibatide, DMP728, and XJ735 could displace I-125-echistatin (IC50 approximate to 0.1-1.5 muM). These results indicate that RGD peptidomimetics have a specificity limited to alpha (IIb)beta (3) integrin, whereas cyclic RGD peptides can also interact with other RGD-dependentintegrins, particularly those of the alpha (v) subunit family.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 23:45:45