Inhibitory action of guanosine 3′,5′-monophosphate on thrombin-induced calcium mobilization in human platelets

Kawahara, Yasuhiro; Yamanishi, Junji; Fukuzaki, Hisashi

doi:10.1016/0049-3848(84)90181-6

Cited by 54 publications

(20 citation statements)

References 16 publications

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“…These include: rapidly occurring changes such as phosphorylation of a 50kD protein by the cyclic GMP-dependent protein kinase (Halbrugge et al, 1990), cyclic GMP-dependent protein phosphorylation/dephosphorylation of myosin light chain (Kawahara et al, 1984) or inhibition of phosphorylation of a 44 kD protein by protein kinase c (Waldmann & Walter, 1989) or long term changes such as activation of platelet ADP ribosyltransferase which seem to be independent of guanylate cyclase stimulation (Brune & Lapetina, 1989). At present however, there is no evidence for the involvement of a particular biochemical pathway in maintaining the inhibition of platelet aggregation by NO or NO-donors.…”

Section: Discussionmentioning

confidence: 99%

The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO‐donors

Salvemini¹,

Radziszewski²,

Korbut³

et al. 1990

British J Pharmacology

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1 Full inhibition of thrombin-induced platelet aggregation was elicited by the least maximal platelet inhibitory concentrations of nitric oxide (NO; 7 + 1 pM) or NO-donors which included sodium nitroprusside (NaNp; 80 + 13 pM), 3-morpholinosydnonimine (SIN-1; 3 + 0.1 pM) or endothelial cells (EC; 2.36 + 0.12 x 105) added min before thrombin. Oxyhaemoglobin (oxyHb; 10pM) administered 30s to 10min after stimulation with thrombin caused a time-dependent reversal of the inhibition induced by these agents. OxyHb was ineffective when these agents were co-incubated with the non-selective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 0.05 mM). 2 OxyHb did not reverse the platelet inhibition with IBMX (0.2mM) or that caused by a selective guanosine 3': 5'-cyclic monophosphate (cyclic GMP) phosphodiesterase inhibitor 2-O-propoxyphenyl-8-azapurin-6-one, (M & B 22948; 20,pM). In addition, oxyHb did not reverse the inhibition with iloprost (1 nM) which inhibits platelet aggregation through stimulation of adenylate cyclase.3 The inhibition of platelet aggregation by NO (7 + 1 pM) or NaNp (80 + 13 pM) was accompanied by a 13 fold increase in cyclic GMP levels occurring within 15s of addition of these agents. In the continued presence of NO or NaNp, the reversing effect of oxyHb given 1 min after thrombin was associated with a pronounced decrease in cyclic GMP levels. 4 We conclude that the inhibition of platelet aggregation by activators of guanylate cyclase depends in the first few minutes on continuous stimulation of the enzyme in order to maintain intracellular concentrations of cyclic GMP, except when its breakdown is inhibited. 5 The addition of agents such as oxyHb after the inhibition of platelet aggregation offers another way of investigating the biochemical changes involved in maintaining platelets in an inactive state.

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Section: Discussionmentioning

confidence: 99%

The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO‐donors

Salvemini¹,

Radziszewski²,

Korbut³

et al. 1990

British J Pharmacology

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“…It is known that cGMP and cAMP, acting predominantly via specific protein kinases, block several steps of the agonist-induced elevation of cytosolic calcium, a basic mechanism of platelet activation [44][45][46], thus inhibiting platelet function.…”

Section: Role Of Insulin and Insulin Resistance In The Modulation Of mentioning

confidence: 99%

Pathophysiology of Platelet Resistance to Anti-Aggregating Agents in Insulin Resistance and Type 2 Diabetes: Implications for Anti-Aggregating Therapy

Anfossi¹,

Trovati

2006

CHAMC

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The insulin resistance syndrome, which presents among its many facets obesity and type 2 diabetes mellitus, is a major risk factor for cardiovascular events. Thus, therapeutic guidelines recommend multifactorial treatment programs including, especially in the presence of type 2 diabetes, antiplatelet drugs. Few data, however, are available about the protective effect of antiplatelet therapy in both obese and type 2 diabetic patients. Furthermore, some reports showed a decreased sensitivity to the platelet antiaggregating effect of acetylsalicylic acid in diabetic patients. In the first part of this review, we focused our attention to alterations of platelets from insulin resistant subjects with or without type 2 diabetes, underlining that platelet hyperactivation is explained, at least in part, by: i) a reduced sensitivity to agents exerting an inhibitory modulation of platelet responses, ii) an altered intracellular milieu with elevated cytosolic Ca2+, iii) an enhanced thromboxane A2 synthesis, and iv) an increased number and/or function of GPIIb/IIIa complexes on platelet membranes. Furthermore, oxidative stress, which increases isoprostane production from arachidonic acid, may be involved in platelet hyperactivation, since isoprostanes activate platelets by interplaying with thromboxane receptors. These defects explain why antiplatelet therapy for both chronic atherosclerotic vascular disease and acute coronary syndromes should be specifically tailored in obese, insulin resistant subjects, especially in the presence of type 2 diabetes mellitus. Thus, in the second part of this review we carried out a critical overview of the clinical trials in subjects with metabolic syndrome and type 2 diabetes mellitus with or without macroangiopathy.

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“…Most authors agree that the main effect of cyclic nucleotides is inhibitory and is exerted through activation of the corresponding cyclic nucleotide-dependent protein kinases, i.e., protein kinase G (PKG) 1 for cGMP and protein kinase A (PKA) for cAMP (12)(13)(14)(15)(16), which are involved in the regulation of basic mechanisms of platelet activation, such as agonist-induced increases of cytosolic calcium (12,(15)(16)(17), fibrinogen binding (18 ), and cytoskeleton protein contraction (19 ). Recent evidence indicates, however, that increased concentrations of platelet cGMP are associated with enhanced platelet function (20,21 ).…”

mentioning

confidence: 99%

Platelet Resistance to the Antiaggregatory Cyclic Nucleotides in Central Obesity Involves Reduced Phosphorylation of Vasodilator-Stimulated Phosphoprotein

et al. 2007

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Inhibitory action of guanosine 3′,5′-monophosphate on thrombin-induced calcium mobilization in human platelets

Cited by 54 publications

References 16 publications

The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO‐donors

The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO‐donors

Pathophysiology of Platelet Resistance to Anti-Aggregating Agents in Insulin Resistance and Type 2 Diabetes: Implications for Anti-Aggregating Therapy

Platelet Resistance to the Antiaggregatory Cyclic Nucleotides in Central Obesity Involves Reduced Phosphorylation of Vasodilator-Stimulated Phosphoprotein

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