EXPANSION OF THE CELLULAR CONTENT OF RIBONUCLEOSIDE TRIPHOSPHATES INDUCES CELL SHRINKAGE AND KCL LOSS IN EHRLICH ASCITES TUMOR-CELLS AND INCHINESE-HAMSTER OVARY CELLS

The conversion to corresponding triphosphate derivatives of various ri bonucleosides has been studied in Ehrlich ascites tumor cells and in C hinese hamster ovary cells under conditions that are optimal for cellu lar uptake of orthophosphate. The initial cellular uptake of orthophos phate is followed by a cellular loss of Cl- which might be consistent with a H2PO4-/Cl- exchange mechanism. Subsequent addition of ribonucle osides to the medium leads to cellular accumulation of the correspondi ng triphosphate and to a concomitant loss of KCl and to sustained cell volume reduction. The latter two events are quite unspecific with reg ard to the nucleobase moiety of the ribonucleoside triphosphate accumu lated (adenine, guanine and purine being almost equally effective) and they depend in a rather simple way on the increase of the cellular co ntent of these compounds. The KCl loss seems to depend on opening of t he separate K+ and Cl- channels. The pharmacological profile of the pu tative ion channels could not be identified in spite of experiments wi th conventional blockers. In the case of purine riboside the accumulat ion of the corresponding triphosphate and concomitant loss of KCl and cell water may be followed by a regain of cell volume due to a continu ed 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 volum e increase, The possibility that the nucleoside triphosphate induced o pening of a putative Cl- channel may be due to a direct effect of trip hosphate on a channel protein is discussed. (C) 1997 Elsevier Science B.V.