Partial isolation and function of the prostacyclin regulating plasma factor

Deckmyn, Hans; Zoja, Carla; Arnout, Jozef; Todisco, Andrea; Bulcke, Felix; D'Hondt, L; Hendrickx, Nico; Gresele, Paolo; Vermylen, Jozef

doi:10.1042/cs0690383

Cited by 25 publications

(4 citation statements)

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“…The relevance of this in vitro effect of dipyridamole to the clinical effîcacy of the drug is questionable, since it was obtained in the 10-100 juM range, whereas therapeutic concentrations range from 2 to 6 fjM [3,20]. During the completion of our work, Deckmyn et al reported that dipyridamole did not increase PGI2 production by fresh rat aortic rings, but delayed the exhaustion of the PGl2-forming capacity during répétitive incubations in Tris buffer [25]. Although it is not clear whether the PGI2 measured in that study came from endothelial or smooth muscle cells, the kinetics and dose-dependency of the dipyridamole effect were quite similar to our data, depicted in Fig.…”

Section: Discussionmentioning

confidence: 74%

Dipyridamole and vascular prostacyclin production

Boeynaems¹,

Coevordem

Demolle³

1986

Biochemical Pharmacology

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The action of dipyridamole on the vascular production of prostacyclin (PGI2) has been investigated. Dipyridamole (1-100 microM) did not induce a significant stimulation of PGI2 release in any of the following experimental models: rings of rabbit aorta, cultured endothelial cells from bovine aorta or human umbilical vein, cultured explants of bovine aortic smooth muscle. The activity of known stimuli of PGI2 release (ADP, suloctidil, serotonin) and the capacity of dipyridamole to inhibit adenosine uptake into endothelial cells were carefully checked. Pretreatment of the rabbit aorta with dipyridamole (10-100 microM) prolonged the transient stimulation of PGI2 release induced by mechanical deendothelialization: this effect was probably due to a partial protection of the cyclooxygenase against oxidative self-inactivation. Our largely negative results are consistent with the current theory that the antiplatelet action of dipyridamole is mediated by adenosine and not by PGI2.

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Section: Discussionmentioning

confidence: 74%

Dipyridamole and vascular prostacyclin production

Boeynaems¹,

Coevordem

Demolle³

1986

Biochemical Pharmacology

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“…The antioxidant activity of dipyridamole leads to the inhibition of leukotriene B4 production in vitro by stimulated white blood cells [85]. Moreover, based on its antioxidant properties, dipyridamole was shown to prolong prostacyclin production by ‘exhausted’ vessel walls, preventing the autoinactivation of cyclo‐oxygenase caused by enhanced peroxide formation [86], an activity similar to the so‐called physiological prostacyclin‐regulating plasma factor [87].…”

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confidence: 99%

Anti‐platelet therapy: phosphodiesterase inhibitors

Gresele¹,

Momi

Falcinelli

2011

Brit J Clinical Pharma

253

238

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Inhibition of platelet aggregation can be achieved either by the blockade of membrane receptors or by interaction with intracellular signalling pathways. Cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP) are two critical intracellular second messengers provided with strong inhibitory activity on fundamental platelet functions. Phosphodiesterases (PDEs), by catalysing the hydrolysis of cAMP and cGMP, limit the intracellular levels of cyclic nucleotides, thus regulating platelet function. The inhibition of PDEs may therefore exert a strong platelet inhibitory effect. Platelets possess three PDE isoforms (PDE2, PDE3 and PDE5), with different selectivity for cAMP and cGMP. Several nonselective or isoenzyme-selective PDE inhibitors have been developed, and some of them have entered clinical use as antiplatelet agents. This review focuses on the effect of PDE2, PDE3 and PDE5 inhibitors on platelet function and on the evidence for an antithrombotic action of some of them, and in particular of dipyridamole and cilostazol.

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“…Vascular endothelium is the major source of plasma prostacyclin. Previous studies have shown that plasma stimulates prostacyclin production by endothelial cells (20)(21)(22). Using Remuzzi et al's (23) exhausted human umbilical arterial seg- Table 1.…”

Section: Discussionmentioning

confidence: 99%

Sickle Cell Vaso-occlusive Crisis Is Associated with Abnormalities in the Ratio of Vasoconstrictor to Vasodilator Prostanoids

1995

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Plasma levels of 6-keto-prostaglandin F1 alpha (6kPGF1 alpha) and thromboxane (Tx) B2 have been assessed in sickle cell disease (SCD) with discrepant results. Inasmuch as direct measurement of plasma prostanoids is fraught with the problem of interfering substances, we assessed plasma 6kPGF1 alpha and TxB2 levels in patients with SCD by RIA after extraction of eicosanoids and separation by HPLC. We demonstrate that the 6kPGF1 alpha and TxB2 levels in children with SCD in steady state as well as in vaso-occlusive crisis (VOC) are significantly lower when compared with those from age-matched controls. The VOC plasma 6kPGF1 alpha and TxB2 levels were, however, significantly elevated when compared with those from children in steady state. Changes similar to those noted with unpaired plasma samples were also observed when paired steady state and VOC plasmas from the same patients were assessed. The ratio of TxB2 to 6kPGF1 alpha was, however, significantly elevated in patients with SCD in crisis when compared with eicosanoid ratios obtained during steady state. In an attempt to understand whether the abnormality in 6kPGF1 alpha was due to an impairment in endothelial cell prostacyclin-regenerating ability, we compared the ability of plasma from controls and children with SCD to activate arachidonic acid (AA) release and prostacyclin production by [14C]AA-prelabeled bovine aortic endothelial cells. Our results suggest that the decreased 6kPGF1 alpha levels in plasma from children with SCD was not due to an effect on substrate AA release but rather a modulatory effect of sickle plasma components on endothelial cell cyclooxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Partial isolation and function of the prostacyclin regulating plasma factor

Cited by 25 publications

References 0 publications

Dipyridamole and vascular prostacyclin production

Dipyridamole and vascular prostacyclin production

Anti‐platelet therapy: phosphodiesterase inhibitors

Sickle Cell Vaso-occlusive Crisis Is Associated with Abnormalities in the Ratio of Vasoconstrictor to Vasodilator Prostanoids

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