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.