Adenine nucleotide metabolism of blood platelets VI. Subcellular localization of nucleotide pools with different functions in the platelet release reaction

Holmsen, Holm; Day, H. James; Storm, Eva

doi:10.1016/0005-2787(69)90003-3

Cited by 160 publications

(54 citation statements)

References 29 publications

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“…Note that the granule fractions also contain metabolic ATP and ADP localized in the mitochondria (less than 3% of total metabolic ATP and ADP, Ref. 19). …”

Section: Analysis Of Metabolic Parametersmentioning

confidence: 99%

Metabolic energy is required in human platelets at any stage during optical aggregation and secretion

Verhoeven¹,

Mommersteeg²,

Akkerman³

1984

Biochimica et Biophysica Acta (BBA) - General Subjects

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The relationship between metabolic energy and platelet aggregation and secretion was investigated by sudden exhaustion of the cell energy content after these platelet responses had been initiated. In normal platelets, optical aggregation was at any stage susceptible to energy exhaustion, whereas single platelet disappearance and secretion were hardly affected. Prelowering the platelet energy content, while preserving the adenylate energy charge, made both optical aggregation and the secretion from dense, a-and acid hydrolase-containing granules susceptible to energy exhaustion, but single platelet disappearance was not affected. Complete arrest of secretion occurred when the energy content had fallen below 3-3.5 pmol ATP equivalents (ATPeq)/10 u platelets, while optical aggregation was interrupted below 2-2.5 pmol ATPeq/I0 n platelets. At any stage of optical aggregation and the three secretion responses, the dependence on energy remained the same, indicating a tight coupling between these functions and metabolic energy, which held during the entire responses.

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“…Note that the granule fractions also contain metabolic ATP and ADP localized in the mitochondria (less than 3% of total metabolic ATP and ADP, Ref. 19). …”

Section: Analysis Of Metabolic Parametersmentioning

confidence: 99%

Metabolic energy is required in human platelets at any stage during optical aggregation and secretion

Verhoeven¹,

Mommersteeg²,

Akkerman³

1984

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…At least 80-90% of release has occurred by 15 sec. By' 30 sec, the total amount of releasable nucleotides and calcium, amounting to approximately 60% of the platelet's total content of these substances (20), appears in the extracellular medium. Incubation to 5 min does not change these levels.…”

Section: Cmentioning

confidence: 99%

Thrombin-Induced Increase in Intracellular Cyclic 3′,5′-Adenosine Monophosphate in Human Platelets

Droller¹,

Wolfe

1972

J. Clin. Invest.

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A B S T R A C T The present data disagree with earlier suggestions that thrombin's effect on platelets is to cause a decrease in intracellular cyclic 3',5'-adenosine monophosphate. Washed humani platelets or plateletrich plasma were incubated at 37°C with human thrombin. After centrifugation, the supernates were assayed for nucleotides and calcium released. The platelet pellets, anid in some experiments the supernates as well, were assayed by radioiimmunoassay for intracellular cyclic AMP. In the washed platelet systenm, increasing doses of thrombin to 0.5 U/cc induced increasing release of nucleotides and calcium. This was accompanied by an average twofold increase in intracellular cyclic AMP levels. Prostaglandin E1, which inhibited 30-50% of release, induced a four-to fivefold increase in cyclic AMP levels that was additive to the cyclic AMP-stimulatory effect of thrombin. Theophylline. which inhibited only 20-40%4 of nucleotide release, was synergistic with thrombin in the intracellular accumulation of cyclic AMP. The timiie-course of cyclic AMP accumulation in response to thrombinl was slower thani thrombin-induced nucleotide release. Similar findings were made in the platelet-rich plasma system where thrombin stimulation of nucleotide release also resulted in a marked accumulation of intracellular cyclic AMP. Thrombin did not appear to stimiiulate the release of intracellular cyclic AMP.The mechanism underlying these observations was not apparent. The thrombin had no measurable inhibitory effect on platelet phosphodiesterase activity in either intact washed cells or the platelet homogenate supernates. Furthermore, thrombin inhibited, rather than stimulated, platelet adenyl cyclase activity in both

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“…The tubes were centrifuged at 100 g for 12 min and the platelet-rich supernatant was kept at room tempera- The aggregating agents were adrenaline (1 liM), ADP (1 or 2 pM), and 0.01 ml of the collagen preparation of Holmsen, Day & Storm (1969). They were added to the platelet-rich plasma to give a final volume of 0.4 ml.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Adrenaline‐induced Platelet Aggregation by the Α‐adrenoceptor Blocking Drug Benextramine

Belleau

Benfey

Melchiorre³

et al. 1982

British J Pharmacology

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The activity of the irreversible α‐adrenoceptor blocking drug, benextramine, was determined in human platelets. Compared to its postsynaptic and presynaptic α‐adrenoceptor blocking potency, benextramine had a very low potency as an antagonist of adrenaline‐induced platelet aggregation. The results confirm the previous observation with the irreversible α‐adrenoceptor blocking drug, phenoxybenzamine, that platelet α‐adrenoceptors differ from postsynaptic and presynaptic α‐adrenoceptors.

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Adenine nucleotide metabolism of blood platelets VI. Subcellular localization of nucleotide pools with different functions in the platelet release reaction

Cited by 160 publications

References 29 publications

Metabolic energy is required in human platelets at any stage during optical aggregation and secretion

Metabolic energy is required in human platelets at any stage during optical aggregation and secretion

Thrombin-Induced Increase in Intracellular Cyclic 3′,5′-Adenosine Monophosphate in Human Platelets

Inhibition of Adrenaline‐induced Platelet Aggregation by the Α‐adrenoceptor Blocking Drug Benextramine

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