Inhibitory mechanism of dipyridamole on platelet aggregation

Fukawa, Kazunaga; Saitoh, Kiyoshi; Irino, Osamu; Ohkubo, Kazumi; Hashimoto, Shuichi

doi:10.1016/0049-3848(82)90080-9

Cited by 18 publications

(8 citation statements)

References 8 publications

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“…Dipyridamole is a phosphodiesterase inhibitor that increases the cyclic AMP by preventing conversion to AMP in platelets [26] . Clopidogrel affects the ADPdependent activation of IIb/IIIa complex via ADP receptor P2Y12 [27] .…”

Section: Resultsmentioning

confidence: 99%

Aqueous Extract of Tournefortia sarmentosa Stem Inhibits ADP-induced Platelet Aggregation

Wang¹,

Tsai²,

Chen³

et al. 2018

pharmaceutical-sciences

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Tournefortia sarmentosa Lam. (Boraginaceae) is a Chinese herbal medicine with antioxidant activities, detoxicating qualities and antiinflammatory uses [1-3]. Numerous pharmacological observations have shown therapeutic effects. Lin et al. revealed that isolated components from the stems of T. sarmentosa decreased Cu 2+-induced low-density-lipoprotein oxidation [1]. Teng et al. investigated the hepatotoxicity effects of T. sarmentosa stem extract and found that it reduced elevated levels of liver function markers, including serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase, and alkaline phosphatase (ALP). It also reduced levels of inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in acetaminophen-intoxicated rats [2]. However, some results measured the inflammatory cytokine expression in cells treated with T. sarmentosa stem extract are contradictory. For example, extracts of T. sarmentosa enhanced the release of cytokines, including IL-6, IL-8, and TNF-α [4] and increased phagocytosis by macrophages and neutrophils [4-5]. Various pharmacologically active compounds from aqueous stem extract of T. sarmentosa have been identified [3] and these components play roles in immune or detoxification regulation. For example, salvianolic acid A, isosalvianolic acid C, and rosmarinic acid exhibited roles in reducing reactive oxygen species activity [1]. Caffeic acid increased the phagocytic ability of macrophages and neutrophils by increasing phosphorylated p38 MAPK or AKT, respectively [4-5]. Salvianolic acid inhibited phagocytic ability of macrophages by suppressing lipopolysaccharideinduced ERK1/2 phosphorylation [4]. These results

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Section: Resultsmentioning

confidence: 99%

Aqueous Extract of Tournefortia sarmentosa Stem Inhibits ADP-induced Platelet Aggregation

Wang¹,

Tsai²,

Chen³

et al. 2018

pharmaceutical-sciences

View full text Add to dashboard Cite

show abstract

“…Platelet aggregation was measured by continuously recording the light transmission of the washed platelet suspension at 660 nm under stirring at 37°C using an aggregometer (RAM-11, Rikadenki Kogyo Co., Tokyo, Japan) as described previously (Fukawa et al, 1982).…”

Section: Platelet Aggregationmentioning

confidence: 99%

In vitro effect of a thymic epithelial culture supernate or thymosin fraction 5 on rabbit platelet aggregation and intracellular cyclic AMP levels

Hashimoto

Itoh

Kawaguchi

et al. 1987

Journal Cellular Physiology

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Supernates of thymic epithelial cell culture (STEC) strongly inhibit aggregation induced by addition of adenosine diphosphate (ADP: 1 microM) or thrombin (0.5 unit per ml) to washed platelet suspensions and accelerated the restoration from ADP-triggered aggregation. At the same time, STEC increased the level of platelet adenosine 3',5'-cyclic monophosphate (cyclic AMP) in a dose-dependent manner. Depending on the concentration used, thymosin fraction 5 increased the level of intracellular cyclic AMP ranging between 5 and 100 micrograms per ml, as well as inhibiting ADP-induced platelet aggregation. The activities of both STEC and thymosin fraction 5 were found to act exclusively on cyclic AMP phosphodiesterase activity in platelets. In contrast the supernates from Chang, HeLa, or HCC-M cells did not affect platelet aggregation induced by ADP, but slightly increased the cyclic AMP level (Chang, HeLa). Within 2 min after the treatment with STEC, more than 50% of the maximum inhibitory activity on platelet aggregation and increases in intracellular cyclic AMP were observed. These activities disappeared following STEC treatment with pronase E. STEC activity was found predominantly in the 1,000-50,000-dalton fractions. These activities were not altered when STEC was treated by adenosine deaminase. The level of prostaglandin E (PGE) derivatives in STEC was about two times that found in the control culture medium. These data suggest that the biological activity of STEC in the platelets might be attributed to thymosinlike polypeptides and PGE1.

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“…Dipyridamole is approved for use clinically because of its anti‐platelet effects (Fukawa et al . 1982; Bult et al .…”

mentioning

confidence: 99%

“…Dipyridamole is approved for use clinically because of its anti-platelet effects (Fukawa et al 1982;Bult et al 1991), but it has also been shown to possess anti-proliferative activities on vascular smooth muscle cells (Himmelfarb & Couper 1997;, fibroblasts (Hewitson et al 2002) and peritoneal mesothelial cells (Hung et al 2001). The combined antiplatelet and antiproliferative properties make dipyridamole a potentially useful drug to prevent vascular stenosis.…”

mentioning

confidence: 99%

Mechanism of Dipyridamole's Action in Inhibition of Venous and Arterial Smooth Muscle Cell Proliferation

Zhuplatov

Masaki

Blumenthal

et al. 2006

Basic Clin Pharma Tox

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Dipyridamole is a potential pharmacological agent to prevent vascular stenosis because of its antiproliferative properties. The mechanisms by which dipyridamole inhibits the growth of vascular smooth muscle cells, especially venous smooth muscle cells, are unclear. In the present study, dipyridamole transiently but significantly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in human venous and arterial smooth muscle cells in a time-and dose-dependent manner. Peak concentrations of both cyclic nucleotides were achieved at 15-30 min. and correlated with inhibition of proliferation in both cell types. The antiproliferative effects of dipyridamole observed at 48 hr were similar whether drug exposure was only 15 min. or sustained for 48 hr. Specific competitive inhibitors of protein kinases A and G attenuated the antiproliferative effects of subsaturating concentrations of dipyridamole, with the effects of protein kinase inhibition being particularly pronounced in venous smooth muscle cells. Flow cytometry analysis showed that dipyridamole caused an enrichment of cells in G 0 /G 1 and a corresponding reduction of cells in S phase. These data indicate that a transient increase in cGMP and cAMP is sufficient to induce downstream kinase activation and subsequent cell cycle arrest, and that protein kinase G may be more important than protein kinase A in mediating the growth inhibitory effect of dipyridamole in venous protein kinase.

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Inhibitory mechanism of dipyridamole on platelet aggregation

Cited by 18 publications

References 8 publications

Aqueous Extract of Tournefortia sarmentosa Stem Inhibits ADP-induced Platelet Aggregation

Aqueous Extract of Tournefortia sarmentosa Stem Inhibits ADP-induced Platelet Aggregation

In vitro effect of a thymic epithelial culture supernate or thymosin fraction 5 on rabbit platelet aggregation and intracellular cyclic AMP levels

Mechanism of Dipyridamole's Action in Inhibition of Venous and Arterial Smooth Muscle Cell Proliferation

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