ADP-Induced changes in [32P]phosphate labeling of phosphatidylinositol-4,5-bisphosphate in washed rabbit platelets made refractory by prior ADP stimulation

Leung, Nick; Vickers, J D; Kinlough-Rathbone, R L; Reimers, Hans-Joachim; Mustard, J. F.

doi:10.1016/0006-291x(83)91751-5

Cited by 24 publications

(7 citation statements)

References 25 publications

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“…5 /SM), the changes in the phosphoinositides and inositol phosphates were similar to those seen in previous studies with 1O,M-ADP (Vickers et al, 1982(Vickers et al, , 1986aLeung et al, 1983). The small decrease in PIP2, compared with that caused by 10 ,tM-ADP used previously (Vickers et al, 1982(Vickers et al, , 1986a, was consistent with the low concentration of ADP used, and the failure of the decrease to be significant may reflect the sensitivity of the assay methods.…”

Section: Discussionsupporting

confidence: 72%

“…These data are compatible with an effect ofadrenaline on the interconversion of PI and PIP and degradation of PIP and PI by phospholipase C to DG, which can be phosphorylated to PA. In contrast with the action of ADP (Vickers et al, 1982(Vickers et al, , 1986aLeung et al, 1983), adrenaline did not cause detectable changes in PIP2.…”

Section: Discussionmentioning

confidence: 63%

“…Although adrenaline alone did not cause large changes in the phosphoinositides and their degradation products, there were changes that may be significant in adrenaline potentiation of ADP-induced aggregation. Adrenaline (Leung et al, 1983;Vickers et al, 1986b), the increased labelling could reflect increased turnover of these molecules. These data are compatible with an effect ofadrenaline on the interconversion of PI and PIP and degradation of PIP and PI by phospholipase C to DG, which can be phosphorylated to PA.…”

Section: Discussionmentioning

confidence: 99%

“…Since the decrease in amount of PIP2 was much smaller than the increase in amount of PIP, the major cause of the increase in PIP appears to have been increased synthesis of PIP from PI. Since the 32P specific radioactivity of ATP is higher than that of the phosphoinositides (Leung et al, 1983, Vickers et al, 1986b PIP and PI by phospholipase C in ADP-stimulated platelets. In platelets prelabelled with [3H]glycerol, the specific radioactivity of the phosphoinositides is higher than that of PA (Vickers et al, 1986b) and thus synthesis of PA from DG formed by degradation of PIP or PI would account for the increased specific radioactivity of PA.…”

Section: Discussionmentioning

confidence: 99%

“…ADP, which stimulates platelet aggregation without causing the secretion of platelet dense-granule contents, causes early changes in phosphoinositides; some of these changes may be due to elevation of cytosolic [Ca2+] (Lloyd et al, 1972(Lloyd et al, , 1973aLeung et al, 1983;Vickers et al, 1982Vickers et al, , 1986a. Turnover of PI has been found to be associated with stimulation of platelets by adrenaline (Deykin & Snyder, 1973;Wallace et al, 1982), although the times of incubation were long, making it difficult to link the PI changes with aggregation.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of phosphoinositide metabolism in potentiation by adrenaline of ADP-induced aggregation of rabbit platelets

Keraly¹,

Vickers²,

Kinlough-Rathbone³

et al. 1987

Biochemical Journal

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Changes in phosphoinositide metabolism were examined in washed rabbit platelets stimulated with 0.5/tM-ADP, 50,uM-adrenaline, or ADP and adrenaline in combination. Adrenaline does not stimulate platelet aggregation when used alone, but does potentiate aggregation stimulated by ADP. In platelets prelabelled with [32P]P1 and [3H]glycerol, adrenaline was found to potentiate the ADP-induced changes in platelet phospholipids, causing larger increases in the amount and labelling of phosphatidylinositol 4-phosphate (PIP) and phosphatidic acid than was observed with ADP alone. The combination of ADP and adrenaline did not produce a greater decrease in phosphatidylinositol 4,5-bisphosphate (PIP2) than was produced by ADP alone. In platelets prelabelled with [3H]inositol, adrenaline potentiated the increases in labelling of inositol phosphate and inositol bisphosphate stimulated by ADP; no increase in inositol trisphosphate labelling was detected with ADP alone or with the combination of ADP and adrenaline. Phentolamine, an a-adrenergic-receptor antagonist, blocked potentiation by adrenaline of ADP-induced changes in phosphoinositide metabolism. Propranolol and sotalol, ,6-adrenergic-receptor antagonists, augmented the potentiation; this is consistent with the concept that the effect of adrenaline is mediated by ,f-adrenergic receptors. The effect of adrenaline on phosphoinositide metabolism appears to be to potentiate the mechanisms by which ADP causes turnover of PIP and possibly degradation of PI, rather than the mechanism by which PIP2 is decreased.

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