Simulation of extracellular nucleotide hydrolysis and determination of kinetic constants for the ectonucleotidases.

Slakey, Linda L.; Cosimini, K; Earls, J P; ThomasC,; Gordon, Ellen L.

doi:10.1016/s0021-9258(18)66741-9

Cited by 17 publications

(1 citation statement)

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“…Purinergic signalling thus has the capacity to be highly complex, with some surprising and perhaps counterintuitive aspects. To illustrate this, I have used the known properties of ectonucleotidases to calculate the diffusion of ATP and its breakdown products [34,35] in a 2D-plane (Figure 1). This is an elaboration, in two dimensions, of a previous one-dimensional model presented in the context of purines potentially acting as morphogens ( [36]).…”

Section: The Biological Imperatives For Direct Measurement Of Purine Releasementioning

confidence: 99%

Biological insights from the direct measurement of purine release

Dale

2021

Biochemical Pharmacology

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Section: The Biological Imperatives For Direct Measurement Of Purine Releasementioning

confidence: 99%

Biological insights from the direct measurement of purine release

Dale

2021

Biochemical Pharmacology

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Storage, release, uptake, and inactivation of purines

Meghji

1993

Drug Development Research

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Adenine nucleotides are released into the interstitial space during platelet thrombus formation and neurotransmission. ATP has also been reported to be released from the heart and endothelial cells in some studies. Ecto ATPase, ADPase, and 5'-nucleotidase activities capable of hydrolyzing ATP sequentially t o adenosine are present in many cell types and may serve to terminate the actions of the nucleotides. The opposing effects of adenosine and ATP on the same cell types have suggested a modulatory role for adenosine on the actions of extracellular ATP and that the rates of hydrolysis of nucleotides might be regulated. Consistent with this it has been found that the balance between feedforward inhibition of 5'-nucleotidase by ADP andlor ATP and preferential delivery of AMP from ADPase to 5'-nucleotidase determines the rate of adenosine production and that this differs in different cell types. Alternatively, adenosine may be produced intracellularly as a result of an imbalance between energy demand and supply. There are at least two different cytosolic forms of 5'-nucleotidase. Degradation of ATP during increased metabolic activity results in an increase in intracellular AMP concentration. Either cytosolic enzyme has a high Km (2-5 mM) and would thus respond to this increase with a proportional rise in the rate of adenosine production. The nucleoside transporter i s essential to allow the diffusion of adenosine to extracellular receptor sites. In general, adenosine must be taken up via the nucleoside transporter before it is inactivated either by phosphorylation by adenosine kinase in the micromolar range or by deamination by adenosine deaminase at higher concentrations. o 1993 WiIey-Liss, Inc.

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