ADP metabolism in vascular tissue, a possible thrombo-regulatory mechanism

Cooper, Denise R.; Lewis, George; Lieberman, G.E.; Webb, H.; Westwick, John

doi:10.1016/0049-3848(79)90008-2

Cited by 50 publications

(13 citation statements)

References 10 publications

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“…The species variation we have shown also implies that results from endothelial cells or vascular preparations from species other than rat are not directly comparable with our results and the only other study of ADPase in perfused rat lung (Cooper et al 1979), apart from that of Crutchley et al (1978), gave results similar to ours -ADP hydrolysed to AMP with very little adenosine or inosine produced. We are therefore confident that our analysis is not at fault and that the ability of perfused rat lung to hydrolyse AMP, while not totally lacking, is very considerably less than its ability to hydrolyse ADP or ATP.…”

Section: Discussionsupporting

confidence: 64%

The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

Chelliah

Bakhle

1983

Exp Physiol

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SUMMARYThe hydrolysis of ATP, ADP and ANMP was studied in perfused isolated lungs from rats, hamnsters, guinea-pigs and humaps. In rats, ATP and ADP at concentrations up to 1 mm were extensively brQken down to AMP and AMP itself wgs more resistant to further hydrqlysis. This pattern of metabolites was maintained in rat lung perfused with Krebs solution containing albumin. The effects of endogenous sex hormones on ADP metbolism were studied in lungs from female rats at different stages of the oestrous cycle. There were no cycle-related changes observed and in a comparison between sexes, only a small difference between males and females was apparent. Lung effluent from rat lunigs exhibited a low level of ADPase activity. Although hamster lungs metakolized ADP to AMP as did rat lungs, lungs from guinea-pigs and humans metabolized ADP and AMP extensively to adenosine. This difference means that although all species exhibit the ability to inactivate pro-aggregatory ADP, the ability to form the anti.aggregatory adenosine from ADP in the pulmonary vasculature varies markedly between species.

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Section: Discussionsupporting

confidence: 64%

The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

Chelliah

Bakhle

1983

Exp Physiol

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“…Plasma ADP partially controls the size of the thrombus, due to its proaggregating action [1]. Initial studies demonstrated an ADPase activity in rabbit and human aorta with and without atherosclerotic involvement [3,4], in endothelial cell culture [5] and in human and rat platelets [6][7][8], among others. Initial studies demonstrated an ADPase activity in rabbit and human aorta with and without atherosclerotic involvement [3,4], in endothelial cell culture [5] and in human and rat platelets [6][7][8], among others.…”

Section: Introductionmentioning

confidence: 99%

Oral L-arginine administration does not inhibit thrombosis on an experimental model of arterial thrombosis: the effect on the apyrasic activity of the arterial wall

Iturry-Yamamoto

Battastini²,

Martins³

et al. 2006

Blood Coagulation &Amp; Fibrinolysis

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Despite the extensive research on the pharmacology of L-arginine, there are only few data on its antithrombotic properties. We studied the effect of oral L-arginine administration in a model of arterial thrombosis in rabbits divided into three groups: group 1, group without intervention; group 2, control group, treated with normal diet and submitted to the thrombosis-triggering protocol; group 3, treated for 2 weeks with L-arginine (2.25%) prior the protocol. L-Arginine did not alter platelet aggregation nor coagulation parameters but reduced vascular activities of both ADPase (49.1 +/- 8.5 versus 28.9 +/- 8.3 versus 18.8 +/- 10.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA F = 19.21; P < 0.0001) and ATPase (97.8 +/- 15.8 versus 52.1 +/- 11.6 versus 31.9 +/- 16.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA, F = 34.65; P < 0.0001). L-Arginine did not reduce the thrombi area (17.1 mm, 9.02 and 48.07, versus 27.04 mm, 25.4 and 70.39, median, percentile 25 and 75 respectively, P = 0.079; group 2 versus group 3, respectively). In conclusion, oral L-arginine administration did not inhibit thrombosis, and, conversely, it significantly reduced the arterial wall ADPase and ATPase activities. This effect may limit its antithrombotic properties.

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“…At least two protective mechanisms appear to exist to prevent this. First, the lung may continuously produce antiaggregatory prostacyclin (PGI2)' (2)(3)(4); second, the pulmonary vessels possess an active ADPase that rapidly degrades the important mediator of platelet aggregation, ADP (5,6). An additional function of pulmonary ADPase may be to prevent the entry of ADP into the systemic circulation, thereby complementing the postulated systemic antithrombotic functions of PGI2.…”

Section: Introductionmentioning

confidence: 99%

Effects of aspirin and dipyridamole on the degradation of adenosine diphosphate by cultured cells derived from bovine pulmonary artery.

Crutchley¹,

Ryan²,

Ryan³

1980

J. Clin. Invest.

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A B S T R A C T To improve understanding of the mechanisms by which ADP is degraded during passage through the pulmonary vascular bed, we examined cultured endothelial and smooth muscle cells of bovine pulmonary artery for their abilities to metabolize [8-"C]ADP. ADP is rapidly converted to AMP and then to adenosine, hypoxanthine, and inosine. Inosine is the major metabolite produced by endothelial cells. Radioactivity (5-10%) is accumulated intracellularly primarily as ATP. Medium containing 50,.M ADP incubated with endothelial cells rapidly loses its ability to aggregate platelets and becomes antiaggregatory under conditions in which prostacyclin is absent. The antiaggregatory activity is probably the result of accumulated adenosine. 10 ,uM dipyridamole inhibits cellular uptake of radioactivity by >90%, and inosine in the medium is largely replaced by adenosine. This is accompanied by increased antiaggregatory activity ofconditioned medium, which can be matched by authentic adenosine at the same concentration. 1 mM aspirin had no effect on the metabolism of ADP by endothelial cells. Our results suggest: (a) Metabolism of ADP during passage through the lung is mainly the result of endothelial ADPase. (b) ADP released from aggregating platelets can be converted to the antiaggregatory substance, adenosine. Dipyridamole may exert some of its antithrombotic actions by preventing the intracellular uptake ofadenosine, thereby increasing its concentration near the site ofthrombus formation. (c) The ability ofthe vessel wall to degrade ADP should not be compromised by the use of aspirin as an antithrombotic drug. (d) Endothelium may retain some of its antithrombogenicity when prostacyclin generation is impaired.

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ADP metabolism in vascular tissue, a possible thrombo-regulatory mechanism

Cited by 50 publications

References 10 publications

The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

Oral L-arginine administration does not inhibit thrombosis on an experimental model of arterial thrombosis: the effect on the apyrasic activity of the arterial wall

Effects of aspirin and dipyridamole on the degradation of adenosine diphosphate by cultured cells derived from bovine pulmonary artery.

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