Roles for both cyclic GMP and cyclic AMP in the inhibition of collagen‐induced platelet aggregation by nitroprusside*

Jang, Elliott K.; Azzam, J.E; Dickinson, Natalie; Davidson, M.M.L.; Haslam, Richard J.

doi:10.1046/j.1365-2141.2002.03479.x

Cited by 55 publications

(44 citation statements)

References 45 publications

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“…6A, B), which is in accord with reports that the inhibition of agonists-induced platelet aggregation is dependent on inhibition of COX-1 rather than TXAS (Lewis and Watts, 1982;Jang et al, 2002). Because these results suggest that inhibition of TXA 2 by RBLw is responsible for the suppression of microsomal specific COX-1, it is shown that RBLw may be used as a COX-1 inhibitor.…”

Section: Discussionsupporting

confidence: 80%

Water Extract from Rice Bran Fermented with Lactobacillus plantarum Hong Inhibits Thromboxane A2 Production Associated Microsomal Enzyme Activity in Human Platelets

Kim

Hong

Ingkasupart

et al. 2015

BSL

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In this study, we investigated the effect of rice bran water extract fermented with Lactobacillus plantarum Hong (RBLw), on activities of cyclooxygenase-1 (COX-1) and thromboxane A 2 synthase (TXAS), thromboxane A 2 (TXA 2 ) production associated microsomal enzymes and evaluated its the antiplatelet effect. RBLw, containing 13.5 mg of ferulic acid, dose-dependently inhibited ADP-induced platelet aggregation, and inhibited the production of TXA 2 , an aggregation molecule. In addition, RBLw directly inhibited COX-1 activity in a dose-dependent manner, but not TXAS activity in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (72 kDa) and TXAS (60.5 kDa) proteins. These results suggest that RBLw selectively inhibited the activity of COX-1 rather than TXAS to attenuate TXA 2 production in ADP-activated platelets. Thus, we demonstrate that RBLw might have direct COX-1 antagonistic function for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.Key Words: Rice bran fermentation, Thromboxane A 2 , Microsomal fraction, Cyclooxygenase-1, Thromboxane A 2 synthase INTRODUCTIONThe aggregation-inducing molecule thromboxane A 2 (TXA 2 ) plays an important role in agonists (eg. collagen, thrombin, ADP)-induced platelet aggregation (Malmsten et al., 1975;Lewis and Watts, 1982;Li et al., 2010), which can cause cardiovascular diseases such as thrombosis, atherosclerosis and myocardial infarction (Schwartz et al., 1990).When diverse agonists such as collagen, thrombin, and ADP activate platelets, membrane phospholipids (i.e. phosphatidylinositol 4,5-bisphosphate) are broken down, and subsequently produce TXA 2 from arachidonic acid (AA). This potently induces platelet activation and vasoconstriction in an autacodial action (Hamberg et al., 1975;Samuelsson et al., 1978;Gresele et al., 1991). Agonists-produced TXA 2 interacts with its receptor in other platelets in an autacoidal reaction, and subsequently increases intracellular free Ca 2+ , a platelet aggregation-inducing molecule, via G αq of G proteincoupled receptor (Jennings, 2009;Cattaneo et al., 1991;Moriyama et al., 1988 -189 -are cyclooxygenase-1 (COX-1) and thromboxane A 2 synthase (TXAS), which are located in microsomes (Carey et al., 1982). COX-1 produces prostaglandin G 2 (PGG 2 ) from substrate AA, TXAS produces TXA 2 from prostaglandin H 2 (PGH 2 ) that is oxidized from PGG 2 by endoperoxidase.Therefore, inhibition of COX-1 or TXAS is very useful to evaluate an antiplatelet effect of any substance or compound.For instance, COX-1 inhibitor aspirin and TXAS inhibitor ozagrel are being used as anti-platelet agents (Patrono, 2001).Rice bran is produced as a by-product in the rice milling process by a method in which the outer layer of the rice grain is removed. Rice bran is known to have various biological effects, including anti-inflammatory, cholesterol-lowering, antioxidant and anti-diabetic activities ...

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Section: Discussionsupporting

confidence: 80%

Water Extract from Rice Bran Fermented with Lactobacillus plantarum Hong Inhibits Thromboxane A2 Production Associated Microsomal Enzyme Activity in Human Platelets

Kim

Hong

Ingkasupart

et al. 2015

BSL

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“…Epinephrine-mediated α2A-adrenoceptor-coupled Gz signaling alone is known to be incapable of inducing full platelet aggregation, and activation of P2Y12 receptor-coupled Gi signaling, which leads to inhibition of adenylyl cyclase, is required (22)(23)(24). An elevated plasma level of NO has been observed in CA-HY compared to CA-GR (10), and NO is known to raise cAMP levels in platelets (25). However, it is consistent with previous reports that inhibition of cAMP accumulation by epinephrine was not significantly different between epinephrine hypo-responders and epinephrine normal responders (9, 10, 26, 27).…”

Section: Discussionmentioning

confidence: 99%

PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

Kim

Kim²,

Kim³

et al. 2011

BMB Reports

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“…Although it was believed that cGMP inhibits platelet activation by activating PKG, we have shown that PKG in fact plays an important stimulatory role in platelet activation (28,30,36), as PKG knock-out mouse platelets and PKG inhibitor-treated human platelets showed significantly reduced platelet aggregation in response to low dose agonists including soluble agonists thrombin, thromboxane A2, and adhesive proteins VWF and collagen. On the other hand, the inhibitory effects of NO donors and cGMP analogs on human platelets were reversed by inhibitors of cAMPdependent protein kinase (37) and adenylyl cyclase (38), indicating that these effects require elevation of cAMP, possibly induced by inhibition of cGMP-regulated phosphodiesterase 3 (31). Thus, NO exerts biphasic FIGURE 5.…”

Section: Discussionmentioning

confidence: 99%

Stimulatory Roles of Nitric-oxide Synthase 3 and Guanylyl Cyclase in Platelet Activation

Marjanovic

Stojanović

et al. 2005

Journal of Biological Chemistry

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Nitric oxide (NO) stimulates soluble guanylyl cyclase and, thus, enhances cyclic guanosine monophosphate (cGMP) levels. It is a currently prevailing concept that NO inhibits platelet activation. This concept, however, does not fully explain why platelet agonists stimulate NO production. Here we show that a major platelet NO synthase (NOS) isoform, NOS3, plays a stimulatory role in platelet secretion and aggregation induced by low doses of platelet agonists. Furthermore, we show that NOS3 promotes thrombosis in vivo. The stimulatory role of NOS is mediated by soluble guanylyl cyclase and results from a cGMP-dependent stimulation of platelet granule secretion. These findings delineate a novel signaling pathway in which agonists sequentially activate NOS3, elevate cGMP, and induce platelet secretion and aggregation. Our data also suggest that NO plays a biphasic role in platelet activation, a stimulatory role at low NO concentrations and an inhibitory role at high NO concentrations.Development of thrombotic diseases involves the injury or dysfunction of the blood vessel wall and activation of blood platelets (1). Upon exposure to agonists such as thrombin, ADP, collagen, and von Willebrand factor (VWF), 2 platelets become "activated" and aggregate to form primary thrombi (1, 2). Activated platelets secrete large quantities of ADP, serotonin, and other factors that amplify platelet activation and stabilize platelet aggregates (3). Activated platelets also secrete pro-coagulation, pro-inflammatory, and growth factors (3-5). Thus, platelet activation plays a major role not only in acute arterial thrombosis but also in the development of chronic vascular diseases, such as atherosclerosis, which in turn causes thrombosis (1, 6).A major advance in the field of vascular biology in the last century was the discovery of the vessel dilator, nitric oxide (NO) (7-9). NO is a short-lived messenger molecule synthesized from L-arginine by a family of enzymes known as nitric-oxide synthases (NOS). Three isoforms of NOS enzymes are known (10 -12): NOS1 (neuronal NOS), NOS2 (inducible NOS), and NOS3 (endothelial NOS). NOS3 is the major isoform known to be expressed in platelets (13). One of the major functions of NO is to stimulate soluble guanylyl cyclase (sGC) and increase the synthesis of cyclic guanosine monophosphate (cGMP) that serves as a secondary messenger regulating the function of cGMP-dependent protein kinase (PKG), cGMP-dependent ion channels, and cGMP-regulated phosphodiesterases (7). High concentrations of NO can also chemically modify (nitrosylation and nitration) proteins and, thus, affect cell functions in a cGMP-independent manner (7, 14 -16). NO is involved in diverse processes, such as smooth muscle relaxation, neurotransmission, immune responses, and inflammation (7). It has been a prevailing concept that NO, by elevating intracellular cGMP, inhibits platelet activation (8). This concept is supported by data that high concentrations of NO donor compounds inhibit platelet activation (17-19). However, the concept...

show abstract

Roles for both cyclic GMP and cyclic AMP in the inhibition of collagen‐induced platelet aggregation by nitroprusside*

Cited by 55 publications

References 45 publications

Water Extract from Rice Bran Fermented with Lactobacillus plantarum Hong Inhibits Thromboxane A2 Production Associated Microsomal Enzyme Activity in Human Platelets

Water Extract from Rice Bran Fermented with Lactobacillus plantarum Hong Inhibits Thromboxane A2 Production Associated Microsomal Enzyme Activity in Human Platelets

PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

Stimulatory Roles of Nitric-oxide Synthase 3 and Guanylyl Cyclase in Platelet Activation

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