Inhibition of Platelet Activation

Activation of platelets is counteracted by biochemical processes which prevent agonist-induced responses. These are mainly mediated by the signaling molecules cAMP and cGMP, and all substances that induce an increase in one or both of diese are defined as platelet antagonists some of these are listed in table 9.5.1. 

Forskolin stimulates die catalytic subunit of adenylyl cyclase directly, bypassing the G proteins, which makes forskolin a much used substance in experiments with elevated platelet cAMP-levels. A number of agents has been demonstrated to inhibit the cAMP phosphodiesterases in platelets, e.g. papaverine, dipyridamole and the methylxantines 

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Inhibition of platelet activation by NO is not exclusively cGM P-dependent but involves mechanisms independent of cGM P like ribosylation or nitrosylation of proteins. For... 

Fig. 9.1 Nitric oxide mediated inhibition of platelet activation. Abbreviations used NO, nitric oxide EDRF, endothelium-derived relaxing factor GC, guanylyl cyclase PDE, phosphodiesterase cGMP-PK, GMP-dependent protein kinase Raplb, small GTPase Raplb ...

Vascular and hematologic effects Ginkgo exerts vascular effects through at least two mechanisms inhibition of platelet-activating factor (PAF) and nitric oxide mechanisms. Ginkgo extract relaxes the porcine basilar artery in a concentration-dependent and partly endothelium-dependent manner (Chen et al. 1997). It also enhances vasorelaxation created by transmural nerve stimulation in arteries with and without the endothelium intact, and is prevented by nitro-L-arginine, indicating that the effect is mediated by nitric oxide. 

Kurihara K, Wardlaw AJ, Moqbel R, Kay AB. (1989). Inhibition of platelet-activating factor (PAF)-induced chemotaxis and PAF binding to human eosinophils and neutrophils by the specific ginkgolide-derived PAF antagonist, BN 52021. J Allergy Clin Immunol. 83(1) 83-90. 

The stereochemistry of the DKP moiety seems to play an important role in the inhibition of platelet-activating factor (PAF) activity. ... 

Inhibition of platelet activating factor (bronchoconstrictor and pro-inflammatory actions). 

It has beat proposed that possible mechanisms underlying the neuroprotective and/or neurotrophic properties of EGb in the CNS indude influences on neurotransmitters, energy metabolism and membrane functions, as well as antioxidant activities and inhibition of platelet-activation factor (PAF). 

In 45 patients with acute coronary syndrome randomized to receive either atorvastatin 10 mg/day or pravastatin 40 mg/day neither atorvastatin nor pravastatin significantly affected clopidogrel-induced inhibition of platelet activation nor did clopidogrel affect the therapeutic efficacy of atorvastatin (84). 

Viable, fertile mild platelet dysfunction with megakaryocyte hyperplasia, increased collagen/ thrombin activation, impaired cyclic nucleotide mediated inhibition of platelet activation (Aszodi et al. 1999 Hauser et al. 1999). 

Langford EJ, Brown AS, Wainwright RJet al (1994) Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty. Lancet 344 1458-1460. 

Burroughs SF, Johnson GJ. Beta-lactam antibiotic-induced platelet dysfunction evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin. Blood 1990 75(7) 1473-80. 

The inhibition of platelet activation is a critical component in the treatment and prevention of cardiovascular diseases and cerebral ischemia/thrombotic disorders. Nitric oxide and prostacyclins inhibit platelet activation by elevating intracellular levels of both cGMP and cAMP, respectively. In platelets, the most abundant PDE is PDE3A, which lowers the intracellular concentration of cAMP. Inhibitors of PDE3A serve as potential antiplatelet agents by elevating cAMP levels. One PDE3-type selective inhibitor cilostazol, which has both antiplatelet, antithrombotic, and vasodilatory effects, is used for the treatment of intermittent claudication and for the prevention of short- and medium-term vessel closure (22). 

Inhibition of platelet-activating factor binding to rabbit platelets was observed after treatment with greater galangal (Jantan et al. 2005). 

Chang, W.C., and RL. Hsu. 1991. Inhibition of platelet activation and endothelial cell injury by flavan-3-ol and saikosaponin compounds. Prostaglandins Leukotrienes Essent. Fatty Acids 44(l) 51-56. 

Langford, E., Brown, A., de belder. A., Smith, R., Martin, J., Wainwright, R., Thomas, M., Radomski, M., Moncada, S., 1994. Inhibition of platelet activity by 5-nitrosoglutathione during coronary angioplasty. The Lancet 344, 1458-1460. 

Flavonols induce cardioprotective effects, including antioxidant effects (protectiOTi against LDL oxidation) and inhibition of platelet activity and vasodilatatimi [48, 69], while very little information is available on their potential anticancer effects. 

Koch E (2005) Inhibition of platelet activating factor (PAF)-induced aggregation of human thrombocytes by ginkgolides considerations on possible bleeding complications after oral intake of Ginkgo biloba extracts. Phytomedicine 12(1-2) 10-16... 

Many effects mediated by CO-induced activation of sGC/cGMP have been described inhibition of platelet activation and aggregation, smooth muscle relaxation, vasoactive effects, inhibition of cellular proliferation, prevention of apoptosis, and effects on neurotransmission [5, 21, 23, 48],... 

More than 300 papers have been published on the pharmacological properties of this extract [23]. Experimentally documented activity includes increased tolerance to hypoxia in brain tissue, improved learning capacity and memory, inhibition of platelet activator factor (PAF) [24], improved cerebral and peripheral circulation, neuroprotective effects [25], and reduction of retinal edema. Although all the constituents of the ginkgo extract are considered to contribute to the therapeutic effects, the ginkgo flavonoids are assumed to play an important role that is due to their free radical scavenging capacity. 

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