Wendy Tomlinson

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The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent(More)
BACKGROUND P2Y(12) plays an important role in regulating platelet aggregation and function. This receptor is the primary target of thienopyridine antiplatelet agents, the active metabolites of which bind irreversibly to the receptor, and of newer agents that can directly and reversibly modulate receptor activity. OBJECTIVE To characterize the receptor(More)
Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y(12) receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large(More)
P2Y receptor activation in many cell types leads to phospholipase C activation and accumulation of inositol phosphates, while in blood platelets, C6-2B glioma cells, and in B10 microvascular endothelial cells a P2Y receptor subtype, which couples to inhibition of adenylyl cyclase, historically termed P2Y(AC), (P2T(AC) or P(2T) in platelets) has been(More)
Alveolar macrophages have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). In this setting they are routinely exposed to cigarette smoke and a range of pathogens including bacteria and viruses. The gene expression changes that result from these challenges may contribute to the initiation and progression of the disease.(More)
Intravenous infusion of L-NG-nitro-arginine, an inhibitor of endothelial nitric oxide (NO) synthesis, produced vasoconstriction in the coronary, cerebral, renal and duodenal vascular beds of the conscious rabbit. In this study, using radiolabelled microspheres, we provide in vivo evidence for a basal NO-dependent vasodilator tone in the coronary vascular(More)
1. ADP-dependent platelet aggregation is mediated by the P2T-purinoceptor and is specifically inhibited by ATP, which is a competitive P2T-purinoceptor antagonist. However, ATP functions as an agonist at other P2-purinoceptor subtypes in other tissues and is, therefore, non-selective. This paper describes the effects of the novel ATP analogue, FPL 66096(More)
We examined the effect of substance P, a potent stimulator of endothelium-derived relaxing factor (EDRF) release, on responses to collagen and adenosine 3',5'-diphosphate (ADP) in an in vivo model of platelet aggregation. Substance P inhibited platelet aggregation induced in vivo by both collagen and ADP. This anti-platelet effect was particularly(More)
Three experiments were performed to determine the behavioral effects of acutely administered chlordimeform (1-56 mg/kg, i.p.) to male mice. In Experiment I, dosages of 30 and 56 mg/kg decreased the amount of time spent investigating a female conspecific. In Experiment II, large dosages of chlordimeform (30 and 56 mg/kg) decreased vertically directed(More)
BACKGROUND During aging, there is a decreased ability to maintain skeletal muscle mass and function (sarcopenia). Such changes in skeletal muscle are also co-morbidities of diseases including cancer, congestive heart failure and chronic obstructive pulmonary disease. The loss of muscle mass results in decreased strength and exercise tolerance and reduced(More)