Effect of calcium and calcium antagonists on [3h]-paf-acether, binding to washed human platelets

Wade, P.J.; Lunt, David O.; Lad, Nagin; Tuffin, D.P.; Mccullagh, Kja

doi:10.1016/0049-3848(86)90233-1

Cited by 30 publications

(13 citation statements)

References 18 publications

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“…In the same series of experiments we demonstrated that D-cis-diltiazem was inactive (IC50 >> 200 ~tM) against thrombin, ADP, and vasopressin-induced rise of platelet [Ca++]i [38]. Subsequently, Wade et al [39] have demonstrated that diltiazem and verapamil inhibits 3H-PAF binding to human platelets, with ICs0s very similiar to those which we have reported for inhibition of PAF-induced platelet aggregation. Therefore the above results together, suggest that diltiazem and verapamil are inhibiting PAF induced elevation of [Ca+ § because they are PAF receptor antagonists as opposed to platelet calcium channel antagonists.…”

Section: Calcium Influx Mechanisms A) Voltage-operated Channels (Voc)supporting

confidence: 71%

Mechanisms of calcium homeostasis in the polymorphonuclear leucocyte

Westwick

Poll

1986

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Section: Calcium Influx Mechanisms A) Voltage-operated Channels (Voc)supporting

confidence: 71%

Mechanisms of calcium homeostasis in the polymorphonuclear leucocyte

Westwick

Poll

1986

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“…Recent studies have demonstrated that agents which modulate PAF-induced calcium flux may exert their effects in part by inhibiting PAF binding [9,13]. To examine this possibility washed human platelets (2 x 108/ ml) were incubated for 20 min at 37°C with 1 ,sM-PMA, -OAG or -PGI2, with 100 nm unlabelled PAF or with buffer.…”

Section: Modulation Of Paf Bindingmentioning

confidence: 99%

Modulation of platelet-activating-factor-induced calcium influx and intracellular calcium release in platelets by phorbol esters

Valone

Johnson

1987

Biochemical Journal

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The mechanisms by which platelet-activating factor (PAF) and thrombin increase intracellular calcium were examined. Platelets were loaded with the calcium-sensitive fluorescent probe Quin 2 and then were suspended in buffer containing 0.5 mM-Mn2" in order to quantify simultaneously calcium release from intracellular stores and divalent cation influx. Pretreating platelets with agents which activate protein kinase C [the phorbol ester phorbol myristate acetate (PMA) or the diacylglycerol l-oleoyl-2-acetylglycerol (OAG)] inhibited increased intracellular calcium by PAF and thrombin in a dose-related manner. That protein kinase C regulates intracellular calcium by phosphorylating proteins in two distinct pathways was suggested by two observations. PAF-induced calcium release was more sensitive to inhibition by PMA and OAG than was manganese influx and the kinetics of recovery from inhibition were different for the two pathways. Both PMA and OAG aggregated Quin 2-loaded platelets without eliciting measurable increases in intracellular calcium. In contrast, prostacyclin, which increases intracellular cyclic AMP, inhibited calcium release and influx in parallel, suggesting that this agent acts at a step common to both pathways.

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“…Therefore, beside their specific effects, these agents might have multiple nonspecific effects such as those re ported herein. Other properties have also been described such as potentiation of the antiaggregatory activity of PGD2 [34] or com petitive antagonism of platelet-aggregating 257 factor [40] and of thromboxane At receptors [41]. These multiple effects might explain the reported effect of DHP to have beneficial effects in the treatment of a number of cardio vascular and circulatory disorders and in ex perimental atherosclerosis [42].…”

Section: Discussionmentioning

confidence: 94%

Comparative Inhibitory Effects of Dihydropyridines on Platelet Aggregation, Calcium Uptake and Cyclic AMP Concentration

Blache

Ojeda

1992

Pharmacology

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We studied the in vitro effects of several calcium channel blockers from the dihydropyridine (DHP) family on platelet aggregation and endogenous serotonin secretion, calcium uptake and cyclic AMP (cAMP) concentration using washed rat platelets. We found that, after 1 min incubation, nifedipine (Nil), nitrendipine (Nit) and nisoldipine (Nis) inhibited the thrombin-induced platelet aggregation and serotonin secretion with IC50 of about 140, 5 and 2 μmol/l, respectively. Nis and Nit are thus much more active than Nif. We also found that the thrombin-induced Ca²⁺ uptake amounted to 2,600 ± 326 pmol Ca²⁺/10⁹ platelets in control conditions. In the presence of 10 μmol/l of the DHP, this uptake was decreased by 19, 49 or 77 %, with Nif, Nit or Nis, respectively. Compound BAY K 8644 (BK) with known agonistic properties on the calcium channel had inhibitory effects on the studied parameters. These compounds were in the order of Nif < BK < Nit < Nis. When added to previously aggregated platelets, Nit caused them to deaggregate. These results seem to be similar to those obtained with cAMP analogues or adenylate cyclase activators. The platelet resting cAMP concentration was therefore measured in the presence of the DHP. A nonsignificant increase was found with 20 μmol/l Nif whereas significant increases of 20 and 68 % as compared with controls were obtained with 20 μmol/l Nit and Nis, respectively. Partition studies between platelets and plasma lipoproteins indicated that the effects might be related to the lipophilicity of the compounds. These data suggest that these agents work on platelet activity by multiple effects located intracellularly or at the membrane level. We propose that these effects could work in combination to explain the in vivo potency of these agents in the treatment of cardiovascular disorders.

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Effect of calcium and calcium antagonists on [3h]-paf-acether, binding to washed human platelets

Cited by 30 publications

References 18 publications

Mechanisms of calcium homeostasis in the polymorphonuclear leucocyte

Mechanisms of calcium homeostasis in the polymorphonuclear leucocyte

Modulation of platelet-activating-factor-induced calcium influx and intracellular calcium release in platelets by phorbol esters

Comparative Inhibitory Effects of Dihydropyridines on Platelet Aggregation, Calcium Uptake and Cyclic AMP Concentration

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