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Expansion of the cellular content of ribonucleoside triphosphates induces cell shrinkage and KCl loss in Ehrlich ascites tumor cells and in Chinese hamster ovary cells.

Abstract
The conversion to corresponding triphosphate derivatives of various ribonucleosides has been studied in Ehrlich ascites tumor cells and in Chinese hamster ovary cells under conditions that are optimal for cellular uptake of orthophosphate. The initial cellular uptake of orthophosphate is followed by a cellular loss of Cl- which might be consistent with a H2PO4-/Cl- exchange mechanism. Subsequent addition of ribonucleosides to the medium leads to cellular accumulation of the corresponding triphosphate and to a concomitant loss of KCl and to sustained cell volume reduction. The latter two events are quite unspecific with regard to the nucleobase moiety of the ribonucleoside triphosphate accumulated (adenine, guanine and purine being almost equally effective) and they depend in a rather simple way on the increase of the cellular content of these compounds. The KCl loss seems to depend on opening of the separate K+ and Cl- channels. The pharmacological profile of the putative ion channels could not be identified in spite of experiments with conventional blockers. In the case of purine riboside the accumulation of the corresponding triphosphate and concomitant loss of KCl and cell water may be followed by a regain of cell volume due to a continued purine riboside triphosphate accumulation, which apparently depends on the uptake of orthophosphate by cotransport with Na+ and which for osmotic reasons is accompanied by the uptake of water and hence volume increase. The possibility that the nucleoside triphosphate induced opening of a putative Cl- channel may be due to a direct effect of triphosphate on a channel protein is discussed.
AuthorsM Marcussen, K Overgaard-Hansen, H Klenow
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1358 Issue 3 Pg. 240-8 (Oct 11 1997) ISSN: 0006-3002 [Print] Netherlands
PMID9366255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chloride Channels
  • Chlorides
  • Potassium Channels
  • Purines
  • Ribonucleotides
  • Guanosine
  • Guanine
  • Potassium Chloride
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Adenine
  • Adenosine
Topics
  • Adenine (metabolism)
  • Adenosine (pharmacology)
  • Adenosine Triphosphate (metabolism)
  • Animals
  • CHO Cells (cytology, metabolism)
  • Carcinoma, Ehrlich Tumor (metabolism, pathology)
  • Chloride Channels (physiology)
  • Chlorides (metabolism)
  • Cricetinae
  • Guanine (metabolism)
  • Guanosine (pharmacology)
  • Guanosine Triphosphate (metabolism)
  • Kinetics
  • Mice
  • Potassium Channels (physiology)
  • Potassium Chloride (metabolism)
  • Purines (metabolism)
  • Ribonucleotides (metabolism)
  • Tumor Cells, Cultured

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