Abstract
The effect of repeated oral administration of ATP on purine transport and metabolism was investigated in rats. An increased ability of the gut to capture intraluminal purine nucleosides and to export ATP and nucleosides toward portal bloodstream was observed in rats after 30 days of treatment with 5 mg/kg/day ATP. This was accompanied in erythrocytes by an increased transport of adenosine rapidly transformed into ATP, which in turn was exported toward extracellular fluid. However, these metabolic changes were associated with a paradoxical and progressive diminution of plasma ATP level below that found in control rats and that was not strictly dependent on the ATP dose administered, whereas plasma adenosine concentration remained unchanged. This diminution likely resulted from an increased ectonucleotidase activity, suggesting that the chronic administration of ATP seems to induce a progressive adaptation of purine metabolism. This adaptive response to free purine supplementation affects both intracellular metabolism and purine exchange between intracellular and extracellular compartments. This modification of free purine turnover and delivery may affect physiological parameters under the control of P1 and P2 purinoceptors described in different experimental models.
Footnotes
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Send reprint requests to: Dr. Ketty Kichenin, Groupe d'Immunologie Denis Diderot, Université Paris 7, Hall des Biotechnologies, Tour 54, CP7124, 2 place Jussieu, 75251 Paris Cedex 05, France. E-mail: Seman{at}paris7.jussieu.fr
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↵1 This work was supported in part by Mayoly Spindler Laboratories (Chatou, France). K.K. was supported by a grant from the Ministere de la Recherche et de la Technologies (CIFRE).
- Abbreviations:
- NT
- nucleoside transporter
- ENT
- equilibrative nucleoside transporter
- NBMPR
- nitrobenzylmercaptopurine
- HBSS
- Hanks' balanced salt solution
- Received December 15, 2000.
- Accepted March 8, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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