Action of hemicholinium-3 on phospholipid metabolism in Krebs II ascites cells

Biochem Pharmacol. 1985 Nov 15;34(22):3987-93. doi: 10.1016/0006-2952(85)90377-6.

Abstract

Incorporation of [Me-14C]choline or/and [2-14C]ethanolamine into phospholipids of Krebs II ascites cells in toto have been tested in the presence of hemicholinium-3. With [Me-14C]choline, labelling of cell pellet, intracellular choline, phosphocholine and total lipid extract is inhibited by hemicholinium-3 in a dose-dependent way between 6.25 X 10(-6) M and 10(-3) M. These effects are caused by a diminution of the choline or/and ethanolamine transport across the cell membrane and by a choline-kinase inhibition. In Krebs cells, choline is taken up by a low affinity Na+ sensitive uptake system (KT = 46 X 10(-6) M) which is competitively inhibited by hemicholinium-3 (KTi = 161 X 10(-6) M). Krebs cells exert a counter-transport (i.e. an exchange of choline across the membrane) against a concentration gradient of 10 mM choline whereas 10 mM hemicholinium-3 has no effect. Choline-kinase is also inhibited (I50 = 57 X 10(-6) M) in Krebs cells in toto and time-course data suggest that choline transport and phosphorylation might be tightly coupled. Specific radioactivities of phosphocholine and choline-glycerophospholipids decrease owing to the effect of the drug on the uptake and phosphorylation system. With 4 X 10(-5) M hemicholinium-3 and [Me-14C]choline as a marker, labelled choline-glycerophospholipids are decreased by 22%. With [2-14C]ethanolamine, labelled ethanolamine-phospholipids are decreased by 26% and choline-glycerophospholipids remain unlabelled. With the two markers, the additional effect produces a 35% decrease. It is concluded that hemicholinium-3 might be able to induce a depression of the intracellular choline and phosphocholine pool which could provoke a serious quantitative deficiency of major phospholipids in Krebs cells.

MeSH terms

  • Animals
  • Carbon Radioisotopes
  • Cells, Cultured
  • Choline / metabolism
  • Ethanolamine
  • Ethanolamines / metabolism
  • Female
  • Hemicholinium 3 / pharmacology*
  • Mice
  • Neoplasms, Experimental / metabolism*
  • Phospholipids / metabolism*
  • Phosphorylation

Substances

  • Carbon Radioisotopes
  • Ethanolamines
  • Phospholipids
  • Hemicholinium 3
  • Ethanolamine
  • Choline