ADP receptor‐induced activation of guanine‐nucleotide‐binding proteins in human platelet membranes

FEBS Journal - Tập 207 Số 1 - Trang 259-263 - 1992
Christian Gachet1, Jean‐Pierre Cazenave1, Philippe Ohlmann1, Gerhard Hilf2, Thomas Wieland3, Karl H. Jakobs3
1INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Centre Régional de Transfusion Sanguine, Strasbourg, France.
2Pharmakologisches Institut, Universität Heidelberg, Federal Republic of Germany.
3Institut für Pharmakologie der Universität GH Essen, Federal Republic of Germany

Tóm tắt

ADP receptor‐regulated binding of the labeled GTP analog, guanosine 5′‐O‐(3‐[35S]thiotriphosphate) ([35S]GTP[γS]), to guanine‐nucleotide‐binding proteins (G proteins) was studied in human platelet membranes. The potent ADP receptor agonist, 2‐methyl‐thio‐adenosine 5′‐diphosphate (2MeSADP), a non‐hydrolyzable analog of ADP, increased the binding of [35S]GTP[γS] without apparent lag phase. Under optimal conditions, i.e. in the presence of GDP (1–10 μM), 2MeSADP increased the binding up to about threefold, with half‐maximal and maximal increase observed at 10 nM and 1 μM 2MeSADP, respectively. ADP itself increased the binding of [35S]GTP[γS] by maximally about twofold, with half‐maximal increase occurring at 0.1 μM ADP. The agonist‐induced stimulation was competitively antagonized by the ADP receptor(s) antagonist, (1S)‐adenosine 5′‐O‐(1‐thiotriphosphate) {(Sp)‐ATP[αS]}. Other platelet receptor agonists known to act through receptors coupled to G proteins also increased binding of [35S]GTP[γS] in human platelet membranes, but without being inhibited by (Sp)‐ATP[αS]. The data presented indicate that the platelet ADP receptor(s) can interact with and efficiently activate G proteins, the nature of which remains to be identified.

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FEBS Journal

Tập 207 Số 1

259-263

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