Inhibition of agonist-induced platelet aggregation, Ca2+ mobilization and granule secretion by guanosine 5′-[β-thio]diphosphate and GDP in intact platelets. Evidence for an inhibitory mechanism unrelated to the inhibition of G-protein-GTP interaction
- 15 February 1988
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 250 (1), 209-214
- https://doi.org/10.1042/bj2500209
Abstract
The effect of guanosine 5′-[beta−thio]diphosphate (GDP[beta S]), reported to be an antagonist of GTP at the G-protein-binding site, on human platelet activation was examined. GDP[beta S] (0.3-3 mM) had significant inhibitory effects on platelet aggregation and 5-hydroxytryptamine (5HT) secretion induced by thrombin, collagen, the thromboxane mimetic U46619 and 1,2-dioctanoylglycerol (diC8) in intact platelets, as well as in saponin-permeabilized platelets. Similar inhibitory effects in intact platelets were also observed with ATP (over similar concentration ranges) and GDP and GTP (at 2- and 10-fold higher concentrations respectively). All four nucleotides also inhibited ADP-induced platelet aggregation in indomethacin-treated platelets under conditions where no 5HT secretion occurred. Inhibition of thrombin-induced aggregation and secretion by GDP[beta S] and ATP in intact platelets was accompanied by a reduction in the thrombin-induced rise in intracellular Ca2+ levels and 45 kDa-protein phosphorylation. The results suggest that at least some of the effects of GDP[beta S] may be unrelated to inhibition of G-protein-GTP interaction, but, instead, may be mediated via an extracellular site, common to all the nucleotides tested and perhaps via inhibition of the effects of endogenous/released ADP. The usefulness of GDP[beta S] as a tool in studying G-protein-GTP interactions in platelets is thus questionable.This publication has 18 references indexed in Scilit:
- 1,2‐Dioctanoylglycerol but not 1‐oleoyl‐2‐acetylglycerol inhibits agonist‐induced platelet responsesEuropean Journal of Biochemistry, 1987
- Inositol 1,4,5-triphosphate-induced granule secretion in platelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptors involves a guanine nucleotide binding protein-dependent mechanism distinct from that of thrombin.JCI Insight, 1987
- Induction of the fibrinogen receptor on human platelets by intracellular mediators.Journal of Biological Chemistry, 1987
- Regulation of the phosphoinositide hydrolysis pathway in thrombin-stimulated platelets by a pertussis toxin-sensitive guanine nucleotide-binding protein. Evaluation of its contribution to platelet activation and comparisons with the adenylate cyclase inhibitory protein, Gi.Journal of Biological Chemistry, 1986
- Effects of guanine nucleotides on the properties of 5‐hydroxytryptamine secretion from electropermeabilised human plateletsEuropean Journal of Biochemistry, 1986
- Inositol 1,4,5-trisphosphate induces aggregation and release of 5-hydroxytryptamine from saponin-permeabilized human platelets.Journal of Biological Chemistry, 1986
- Platelet activation: role of an ADP receptor.1986
- Effect of various excitatory agonists on the secretion of 5‐hydroxytryptamine from permeabilised human platelets induced by Ca2+ in the presence or absence of GTPFEBS Letters, 1985
- DIFFERENCES IN THE MODE OF ACTION OF 1-OLEOYL-2-ACETYL-GLYCEROL AND PHORBOL ESTER IN PLATELET ACTIVATION1985
- MECHANISMS OF PLATELET SHAPE CHANGE, AGGREGATION, AND RELEASE INDUCED BY COLLAGEN, THROMBIN, OR A23,1871977