Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets.

Agranoff, Bernard W.; Murthy, Pushpalatha P. N.; Seguin, Edward B.

doi:10.1016/s0021-9258(18)32882-5

Cited by 381 publications

(12 citation statements)

References 21 publications

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“…phate, but not phosphatidylinositol, form the substrates for phospholipase C attack in a variety of tissues following receptor activation (for review, see Berridge, 1984). A similar conclusion has been reached for human platelets challenged with thrombin (Agranoff et al, 1983;Watson et al, 1984b). Interestingly though, the action of collagen, unlike thrombin, can evoke a significant release of ATP without the apparent mobilization of intracellular Ca2+ as assessed by using the fluorescent Ca2+ probe quin2 (Rink et al, 1983).…”

supporting

confidence: 70%

Collagen stimulates [3H]inositol trisphosphate formation in indomethacin-treated human platelets

Watson¹,

Reep²,

McConnell³

et al. 1985

Biochemical Journal

130

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The present study investigates the pathway of metabolism of inositol phospholipids in human platelets exposed to collagen. Platelet activation by collagen was preceded by a lag phase usually lasting 10-20 s. Formation of [3H]inositol trisphosphate (IP3) was not observed during this period, but occurred in parallel with the onset of aggregation, release of ATP and phosphorylation of a 20 000 Da and a 40 000 Da protein. Indomethacin treatment partially inhibited all of these responses. Aggregation and ATP release, but not IP3 formation, were further inhibited in indomethacin-treated platelets loaded with the fluorescent Ca2+ indicator, quin2. Under these conditions there was no detectable mobilization of Ca2+. These results demonstrate that activation of platelets by collagen is associated with rapid hydrolysis of polyphosphoinositides by phospholipase C, thereby producing IP3. This observation is discussed in relation to IP3 as a possible Ca2+-mobilizing agent.

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supporting

confidence: 70%

Collagen stimulates [3H]inositol trisphosphate formation in indomethacin-treated human platelets

Watson¹,

Reep²,

McConnell³

et al. 1985

Biochemical Journal

130

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“…One of the earliest steps of activation of platelets consists of the phosphodiesteratic cleavage of phosphatidylinositol 4,5-bisphosphate to 1,2-diacylglycerol and inositol 1,4,5-trisphosphate (Agranoff et al, 1983). Whereas the latter has been demonstrated to release Ca2+ from internal membranes (Authi & Crawford, 1985;Brass & Joseph, 1985), the former activates protein kinase C (Kaibuchi et al,.…”

Section: Resultsmentioning

confidence: 99%

Activation of Na+/H+ exchange in human platelets stimulated by thrombin and a phorbol ester

Siffert¹,

Siffert²,

Scheid³

1987

Biochemical Journal

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We have investigated changes in cytoplasmic pH (pHi) in activated human platelets, using the fluorescent probe 2,7-biscarboxyethyl-5(6)-carboxyfluorescein. Stimulation of platelets by thrombin or 12-O-tetradecanoylphorbol 13-acetate increased pHi by about 0.11 pH unit above the resting value. This increase in pHi depended on the presence of external Na+ and was inhibited by ethylisopropylamiloride. The data suggest that protein kinase C mediates Na+/H+ exchange in human platelets.

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“…One of the most potent of platelet agonists is a-throm bin, a serine protease, displaying somewhat complex binding characteristics, which causes a rapid generation of InsP3. Such Ins.P3 has been assayed radioisotopically (Agranoff 1983;Watson 1984) and by mass (Rittenhouse & Sasson 1985). The majority of the mass of InsP3 formed in response to I a, if Jo F ig u re 2.…”

Section: Agonist-induced Generation Of Insp3 In Plateletsmentioning

confidence: 99%

Regulation of platelet phospholipase C

Rittenhouse

Banga

Sasson

et al. 1988

Phil. Trans. R. Soc. Lond. B

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We have investigated factors affecting the activation of phospholipase C in human platelets. Prior exposure of platelets to phorbol esters that stimulated protein kinase C inhibits the activation of phospholipase C in response to a variety of receptor-directed agonists, including alpha- and gamma-thrombin and thromboxane A2 analogues. Such activation has been assayed by measurements of accumulated InsP3 (including Ins(1,4,5)P3 and Ins(1,3,4)P3) and PtdOH. Inhibition is not overcome by Ca2+ ionophores, and substances that block or mimic Na+-H+ exchange neither block nor mimic these inhibitory effects. Cyclic AMP and cyclic GMP, other agents known to inhibit phospholipase C activation, do not accumulate in platelets exposed to phorbol esters. Although a portion of the effects of phorbol ester on InsP3 accumulation may be explained by 5-phosphomonoesterase activity, it is likely that more direct effects on phospholipase C are being exerted as well, and contribute the major inhibitory route. We have examined the susceptibility of adenylyl cyclase-associated Gi and 'Gp'-activated phospholipase C to inhibitory ADP-ribosylation by pertussis toxin-derived enzyme (S1 protomer) administered to saponin-permeabilized platelets. The effects of alpha-thrombin on adenylyl cyclase can be inhibited by up to 50% by S1, at which point inhibition of phospholipase C is barely detectable. Thromboxane A2 analogues, which do not affect adenylyl cyclase (Gi), stimulate phospholipase C; this effect is not impaired by S1. We therefore propose that the inhibitory effects of phorbol esters on the activation of phospholipase C are not mediated primarily by effects on Gi.

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Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets.

Cited by 381 publications

References 21 publications

Collagen stimulates [3H]inositol trisphosphate formation in indomethacin-treated human platelets

Collagen stimulates [3H]inositol trisphosphate formation in indomethacin-treated human platelets

Activation of Na+/H+ exchange in human platelets stimulated by thrombin and a phorbol ester

Regulation of platelet phospholipase C

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