Sub-second oscillations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate during platelet activation by ADP and thrombin: lack of correlation with calcium kinetics

Raha, Sanghamitra; Jones, G D; Gear, Adrian R.L.

doi:10.1042/bj2920643

Cited by 39 publications

(17 citation statements)

References 35 publications

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“…It is likely that the internal release is due to activation of phospholipase C (PLC) resulting in the generation of the Ca 2+ -mobilising messenger inositol 1,4,5-trisphosphate (IP 3 ), but an effect of ADP on phosphoinositide metabolism has not always been demonstrated. Over many years while some authors have reported stimulation of phosphoinositide metabolism by ADP [Lloyd et al, 1972;Daniel et al, 1986;Olbrich et al, 1989;Heemskerk et al, 1993;Raha et al, 1993;Vanags et al, 1998], others have failed to detect it [MacIntyre et al, 1985;Fisher et al, 1985;Vickers et al, 1990;Packham et al, 1993;Pulcinelli et al, 1995]. This variation in results probably reflects the fact that ADP is a rather weaker activator of PLC than might be expected both from its potency as an aggregating agent and from its ability to increase intracellular Ca 2+ [MacIntyre et al, 1985] as well as the difficulty of excluding effects due to other released mediators.…”

Section: P2 Receptors On Plateletsmentioning

confidence: 75%

Discovery and recognition of purine receptor subtypes on platelets

Hourani

2001

Drug Development Research

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The effects of purines on platelets have been known since the 1960s, when Born demonstrated aggregation induced by ADP and its inhibition by adenosine and by ATP. The inhibition by adenosine is not specific for ADP, and adenosine acts at a separate receptor to stimulate adenylate cyclase, which has an inhibitory effect on platelet function. Studies using selective agonists and antagonists have shown that the platelet receptor is of the A 2A subtype and this has been confirmed using A 2A knockout mice. The situation with ADP is more complex, and there has been controversy about the number of ADP receptors on platelets. ADP causes shape change, aggregation, mobilisation of calcium from intracellular stores, rapid calcium influx, and inhibition of adenylate cyclase, and the relationship between these is becoming clearer. Two cloned P2 receptors have been detected on platelets, P2X 1 and P2Y 1 , and a third P2Y receptor is thought to exist. The P2X 1 receptor is responsible for the rapid calcium influx and can be activated by ATP as well as by ADP, but is likely to be desensitised under normal experimental conditions and its pathophysiological role is uncertain. The P2Y 1 receptor is responsible for calcium mobilisation, shape change, and the initiation of aggregation, and these responses are abolished in P2Y 1 knockout mice, while the other P2Y receptor is responsible for inhibition of adenylate cyclase and is required for full aggregation. ATP is a competitive antagonist at both these P2Y receptors, while some nucleotide analogues can discriminate between them. Drug Dev.

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Section: P2 Receptors On Plateletsmentioning

confidence: 75%

Discovery and recognition of purine receptor subtypes on platelets

Hourani

2001

Drug Development Research

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“…Direct evidence that shear forces acting alone can initiate signal-transduction events is known in many cell types, such as for endothelial cells sensing arterial shear forces (Davies, 1995). In addition, our own work has shown that arterial shear forces can induce rapid, brief bursts of 1,4,5-inositol triphosphate and 1,3,4,5-inositoltetrakis phosphate (Raha et al, 1993) in the absence of any increases in cytoplasmic calcium.…”

Section: Influence Of Shear Force On the Kinetics Of Platelet Aggregamentioning

confidence: 97%

“…Even earlier biochemical events have been studied, occurring in the millisecond time domain. ADP-induced calcium channels open by 50 msec (Sage and Rink, 1916), and liberation of inositol phosphates occurs with early peaks near 150 to 200 msec (Raha et al, 1993).…”

Section: Introductionmentioning

confidence: 98%

Platelet adhesion to collagen activates a phosphoprotein complex of heat-shock proteins and protein phosphatase 1

Gear

Simon

Polanowska-Grabowska

1997

J. Neural Transmission

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Rapid activation of blood platelets is required for effective haemostasis, with shape change, aggregation, secretion of granule contents and cell adhesion occurring in seconds or even milliseconds. Signal-transduction events, evidenced by changes in protein phosphorylation and calcium levels, also take place in this time domain. We have now shown that platelet adhesion to collagen via the alpha 2 beta 1 integrin under arterial shear forces initiated the rapid dephosphorylation of a 67 kDa protein "band" which contained the 70 kDa constitutive heat-shock protein, hsc70. Immunoprecipitation with hsc70 antibodies revealed a large phosphoprotein complex in resting platelets and adhesion caused dissociation of the complex along with dephosphorylation of hsc70. The complex also contained the hsp90 heat-shock protein, protein phosphatase IC, alpha, delta and M subunits, and some 7-8 unidentified phosphoproteins. The data suggest that heat-shock proteins and protein phosphatases are actively involved in integrin-mediated platelet adhesion.

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“…This probably reflects their contrasting ability to activate PLC with thrombin stimulating PLC activity more strongly than ADP or indeed other agonists (Table 3). [31][32][33][34] It is known that activation of this enzyme correlates well with the stimulation of platelet aggregation and secretion. Therefore, our results indicate that at least with high-dose thrombin, G␣ q signaling pathways are more critical for aggregation than G i signaling.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a role for Gαi1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Gαi1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder

Patel

Rahman

et al. 2003

Blood

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We have examined platelet functional responses and characterized a novel signaling defect in the platelets of a patient suffering from a chronic bleeding disorder. Platelet aggregation responses stimulated by weak agonists such as adenosine diphosphate (ADP) and adrenaline were severely impaired. In comparison, both aggregation and dense granule secretion were normal following activation with high doses of collagen, thrombin, or phorbol-12 myristate-13 acetate (PMA). ADP, thrombin, or thromboxane A 2 (TxA 2 ) signaling through their respective G qcoupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation. In comparison, G i -mediated signaling induced by either thrombin, ADP, or adrenaline, examined by suppression of forskolin-stimulated rise in cyclic AMP (cAMP) was impaired, indicating dysfunctional G␣ i signaling. Immunoblot analysis of platelet membranes with specific antiserum against different G␣ subunits indicated normal levels of G␣ i2 , G␣ i3 , G␣ z , and G␣ q in patient platelets. However, the G␣ i1 level was reduced to 25% of that found in normal platelets. Analysis of platelet cDNA and gDNA revealed no abnormality in either the G␣ i1 or G␣ i2 gene sequences.

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Sub-second oscillations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate during platelet activation by ADP and thrombin: lack of correlation with calcium kinetics

Cited by 39 publications

References 35 publications

Discovery and recognition of purine receptor subtypes on platelets

Discovery and recognition of purine receptor subtypes on platelets

Platelet adhesion to collagen activates a phosphoprotein complex of heat-shock proteins and protein phosphatase 1

Evidence for a role for Gαi1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Gαi1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder

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