The Platelet of the Newborn Infant – Adenine Nucleotide Metabolism and Release

1980 ◽  
Vol 43 (02) ◽  
pp. 099-103 ◽  
Author(s):  
J M Whaun ◽  
P Lievaart ◽  

SummaryBlood from normal full term infants, mothers and normal adults was collected in citrate. Citrated platelet-rich plasma was prelabelled with 3H-adenine and reacted with release inducers, collagen and adrenaline. Adenine nucleotide metabolism, total adenine nucleotide levels and changes in sizes of these pools were determined in platelets from these three groups of subjects.At rest, the platelet of the newborn infant, compared to that of the mother and normal adult, possessed similar amounts of adenosine triphosphate (ATP), 4.6 ± 0.2 (SD), 5.0 ± 1.1, 4.9 ± 0.6 µmoles ATP/1011 platelets respectively, and adenosine diphosphate (ADP), 2.4 ± 0.7, 2.8 ± 0.6, 3.0 ± 0.3 umoles ADP/1011 platelets respectively. However the marked elevation of specific radioactivity of ADP and ATP in these resting platelets indicated the platelet of the neonate has decreased adenine nucleotide stores.In addition to these decreased stores of adenine nucleotides, infant platelets showed significantly impaired release of ADP and ATP on exposure to collagen. The release of ADP in infants, mothers, and other adults was 0.9 ± 0.5 (SD), 1.5 ± 0.5, 1.5 ± 0.1 umoles/1011 platelets respectively; that of ATP was 0.6 ± 0.3, 1.0 ± 0.1,1.3 ± 0.2 µmoles/1011 platelets respectively. With collagen-induced release, platelets of newborn infants compared to those of other subjects showed only slight increased specific radioactivities of adenine nucleotides over basal levels. The content of metabolic hypoxanthine, a breakdown product of adenine nucleotides, increased in both platelets and plasma in all subjects studied.In contrast, with adrenaline as release inducer, the platelets of the newborn infant showed no adenine nucleotide release, no change in total ATP and level of radioactive hypoxanthine, and minimal change in total ADP. The reason for this decreased adrenaline reactivity of infant platelets compared to reactivity of adult platelets is unknown.Infant platelets may have different membranes, with resulting differences in regulation of cellular processes, or alternatively, may be refractory to catecholamines because of elevated levels of circulating catecholamines in the newborn period.

Blood ◽  
1973 ◽  
Vol 42 (4) ◽  
pp. 557-564 ◽  
Author(s):  
Herman E. Kattlove ◽  
Dorothy Mormino

Abstract The effect of cold on platelet adenine nucleotide (PAN) metabolism was studied. Spontaneous aggregation which occurs when chilled platelet-rich plasma (PRP) is simultaneously warmed and stirred was not accompanied by the changes in adenine nucleotides associated with the release reaction. Connective tissue caused the release of the same amount of ADP and conversion of equal amounts of ATP to IMP and hypoxanthine in cold-stored platelets as it did in room temperature stored platelets. However, cold did have an important effect on PAN. In PRP stored at cold (0° C, 3° C) temperatures and warmed up to 37° C in the presence of 3H adenine, there was an increase in the conversion of adenine to its metabolites and ultimately to hypoxanthine as compared to PRP stored at warmer temperatures. This effect could not be prevented by ouabain, prostaglandin E1, antibody to immunoglobulin M or adenosine.


1971 ◽  
Vol 25 (02) ◽  
pp. 223-233
Author(s):  
M Murakami ◽  
K Odake

SummaryAfter platelet-rich plasma was incubated with radioactive adenine, radioactive adenine nucleotides in platelets were separated by two-dimensional thin-layer chromatography.Radioactive adenine was selectively incorporated into adenine nucleotides. Gradual decomposition of labelled nucleotides was observed after longer period of incubation. Radioactive ATP, ADP, AMP, IMP, and hypoxanthine were separated from PCA extract of platelets. On the other hand, radioactive adenine and hypoxanthine were separated from platelet-poor plasma.After thrombin treatment, radioactive ATP in platelets broke down rapidly, while radioactive ADP decreased more slowly. Radioactive AMP increased at first in the cellular and supernatant fractions, and then decreased gradually. The accumulation of radioactive hypoxanthine was observed in the supernatant fraction. Released radioactive ATP and ADP were 23% and 22% of the initial radioactive ATP and ADP in platelets, respectively.


1976 ◽  
Vol 36 (01) ◽  
pp. 200-207 ◽  
Author(s):  
Donald G. Corby ◽  
Thomas F. Zuck

SummaryPer cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to high dose ADP (20 μM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 μM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns’ PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns’ platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
G. Kocic ◽  
J. Nikolic ◽  
T. Jevtovic-Stoimenov ◽  
D. Sokolovic ◽  
H. Kocic ◽  
...  

L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism:5′-nucleotidase (5′-NU), adenosine deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme,5′-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased5′-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.


1975 ◽  
Vol 33 (02) ◽  
pp. 310-327 ◽  
Author(s):  
Dale H Cowan ◽  
Richard C Graham

SummaryPlatelet ultrastructure, protein composition, and adenine nucleotide metabolism were studied in patients ingesting ethanol to elucidate the mechanism of ethanol-induced changes in platelet function and survival. Serial measurements were made in 2 patients who maintained blood ethanol levels in excess of 300 mg/100 ml for 3 to 4 weeks. No major changes in structure or metabolism were detected in platelets from the patient whose platelet counts remained stable during the ingestion period. By contrast, the development of thrombocytopenia in the other patient was associated with significantly reduced intracellular ADP, increased ATP/ADP ratio, decreased release of ADP, increased specific radioactivity of intracellular ATP and ADP, and increased formation of hypoxanthine. Additionally, platelets from this patient varied markedly in size, contained giant granules, and possessed a poorly defined micro-tubular system. After stimulation with ADP or collagen, centripetal granule migration was retarded, and the aggregates formed were small and loose. Several large proteins were absent from the supernatant fraction of sonicated platelets from the thrombocytopenic patient. Exposure of normal platelets to ethanol in vitro resulted in no detectable change in platelet ultrastructure. The data indicate that the ethanol-related abnormalities of platelet function are due in part to subnormal amounts of intracellular ADP and a deficit in the storage pool of ADP. Additionally, the results suggest that impairment in the release mechanism to the observed defect in the release reaction.


1986 ◽  
Vol 250 (4) ◽  
pp. F720-F733 ◽  
Author(s):  
J. M. Weinberg ◽  
H. D. Humes

The effects of exogenous nucleotides on adenine nucleotide metabolism and cell cation levels in normal and O2-deprived isolated rabbit kidney tubules were studied to gain insight into ways in which exogenous nucleotides could contribute to ameliorating O2 deprivation-induced injury. In control oxygenated tubules, 250 microM exogenous ATP, ADP, or AMP resulted in two- to threefold increases of cell ATP over 75-90 min of incubation and smaller relative increases of ADP and AMP. GTP was not increased. Exogenous adenosine, inosine, and hypoxanthine were substantially less effective at increasing intracellular nucleotides than equimolar concentrations of exogenous nucleotides. Nucleotide-treated cells had higher levels of Ca2+ and Mg2+ than untreated cells. Treatment of O2-deprived tubules with exogenous Mg-ATP improved recovery of ATP levels following O2 deprivation, and tubules with mild injury increased their ATP levels to supranormal values such as those seen in control oxygenated tubules treated with nucleotides. Increases of tubule cell ATP levels required ongoing oxidative metabolism and thus were not evident until the reoxygenation recovery period. Exogenous ATP produced some improvement of other injury-associated metabolic parameters but did not substantially alter the overall pattern of tubule susceptibility to lethal cell injury. Allopurinol did not affect the behavior of oxygenated or O2-deprived tubules irrespective of the presence of exogenous ATP. These data clarify the potential for manipulating intracellular ATP levels with exogenous nucleotides and the functional consequences of such manipulation in oxygenated and O2-deprived renal tubule cells.


1983 ◽  
Vol 245 (5) ◽  
pp. H880-H886
Author(s):  
H. G. Zimmer ◽  
H. Ibel

Continuous iv infusion of ribose for 5 h in unanesthetized and unrestrained rats treated with isoproterenol (25 mg/kg sc) further enhanced the available pool of 5-phosphoribosyl-1-pyrophosphate and the biosynthesis of adenine nucleotides in the myocardium. The increase in adenine nucleotide biosynthesis was of such an extent that the isoproterenol-induced decline of the ATP level (mumol/g) was attenuated after 5 h (isoproterenol + ribose infusion 4.0 +/- 0.2, n = 10; isoproterenol + NaCl infusion 3.5 +/- 0.1, n = 23; control 4.5 + 0.1, n = 38) and prevented after 24 h (isoproterenol + ribose infusion 4.6 +/- 0.3, n = 5; isoproterenol + NaCl infusion 3.2 +/- 0.1, n = 9). Ribose, however, did not affect the isoproterenol-elicited elevation of the adenosine 3',5'-cyclic monophosphate (cAMP) and glucose 6-phosphate content nor did it influence the decline in glycogen. Thus ribose acts primarily via elevation of the cardiac 5-phosphoribosyl-1-pyrophosphate pool. Measurements of hemodynamic parameters with an ultraminiature catheter pressure transducer in intact rats anesthetized with thiobutabarbital sodium revealed that ribose infusion for at least 3 h further enhanced the isoproterenol-elicited increase in left ventricular dP/dtmax by about 20% but did not influence appreciably the rise in heart rate and the fall in left ventricular systolic pressure. Since ribose did not affect the immediate hemodynamic alterations induced by isoproterenol, it appears that it exerts its hemodynamic effects via the pronounced influence on cardiac adenine nucleotide metabolism.


1972 ◽  
Vol 27 (03) ◽  
pp. 416-424
Author(s):  
M Murakami ◽  
K Yoshino ◽  
M Takase ◽  
K Odake

SummaryChanges in platelet adenine nucleotides during collagen-induced aggregation were estimated. Averaged values of ATP and ADP in intact platelets were 56.3 and 28.9 attomoles per platelet, respectively. After collagen-induced aggregation, intracellular ATP plus ADP was depleted to about half of that in intact platelets. The released ADP accounted for 13% of that in intact platelets.Behavior of platelet adenine nucleotides during aggregation was divided into the following phases. At first, platelet ATP decreased without the release of nucleotides. The release of ADP occurred at the stage of rapid change of light transmission. Subsequently, the released ADP decomposed in parallel with the degradation of intracellular ADP. The radioactive ATP in platelets decreased during exposure to collagen, without appreciable release of radioactive nucleotides. The ATP released from disrupted platelets was rapidly metabolized in plasma.


1985 ◽  
Vol 249 (5) ◽  
pp. R603-R610
Author(s):  
J. Turinsky ◽  
I. H. Chaudry

The role of phospholipid and adenine nucleotide metabolism in postburn unresponsiveness of muscle to insulin was examined. A single hindlimb scald in the rat was produced, and 3 days later soleus muscles were incubated in vitro with and without insulin. Under basal conditions muscles from the burned limbs had normal contents of phosphatidylcholine and phosphatidylinositol but decreased diphosphatidylglycerol (-39%) and phosphatidylethanolamine (-24%) and increased sphingomyelin (+62%), lysophosphatidylcholine (+68%), and phosphatidylserine (+13%) compared with the contralateral unburned limb. Such muscle also incorporated 107-396% more [32P]phosphate into all measured phospholipids, except for diphosphatidylglycerol. The presence of insulin had no effect on either the mass of phospholipids or 32P incorporation in any muscle. The burned limb muscles (frozen in situ) also exhibited lower levels of ATP (-25%) and total adenine nucleotides (-24%) than uninjured muscle but normal adenylate energy charge. The burned limb muscles had lower adenosine (-37%), but inosine and hypoxanthine were 82 and 39% higher, respectively. These data suggest recovery of muscle from local thermal injury is associated with alterations in mass, and possibly also turnover, of tissue phospholipids, the measured phospholipids do not mediate the postreceptor action of insulin in normal muscle, energy charge of the recovering injured muscle is restored before ATP level at the time when this muscle is unresponsive to insulin stimulation.


1987 ◽  
Vol 242 (2) ◽  
pp. 551-558 ◽  
Author(s):  
J Spychała ◽  
G Van den Berghe

The turnover of the adenine nucleotide pool, the pathway of the degradation of AMP and the occurrence of recycling of adenosine were investigated in isolated chicken hepatocytes, in which the adenylates had been labelled by prior incubation with [14C]adenine. Under physiological conditions, 85% of the IMP synthesized by the ‘de novo’ pathway (approx. 37 nmol/min per g of cells) was catabolized directly via inosine into uric acid, and 14% was converted into adenine nucleotides. The latter were found to turn over at the rate of approx. 5 nmol/min per g of tissue. Inhibition of adenosine deaminase by 1 microM-coformycin had no effect on the formation of labelled uric acid, indicating that the initial degradation of AMP proceeds by way of deamination rather than dephosphorylation. Inhibition of adenosine kinase by 100 microM-5-iodotubercidin resulted in a loss of labelled ATP, demonstrating that adenosine is normally formed from AMP but is recycled. Unexpectedly, 5-iodotubercidin did not decrease the total concentration of ATP, indicating that the loss of adenylates caused by inhibition of adenosine kinase was nearly completely compensated by formation of AMP de novo. Anoxia induced a greatly increased catabolism of the adenine nucleotide pool, which proceeded in part by dephosphorylation of AMP. On reoxygenation, the formation of AMP de novo was increased 8-fold as compared with normoxic conditions. The latter results indicate the existence of adaptive mechanisms in chick liver allowing, when required, channelling of the metabolic flux through the ‘de novo’ pathway, away from the uricotelic catabolic route, into the synthesis of adenine nucleotides.


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