Regulation of ornithine decarboxylase activity in LoVo cells.
The role of Na+ and Na(+)-H+ exchange in the stimulation of ornithine decarboxylase (ODC) activity has been investigated in a human colon adenocarcinoma cell line, LoVo. Asparagine (Asn; 10 mM) or 10% fetal bovine serum (FBS) increased ODC activity from undetectable levels to greater than 500 pmol CO2.mg protein-1.h-1 in 4 h. This increase could be reduced 50% by concentrations of Na(+)-H+ exchange inhibitors that did not reduce protein synthesis. (approximately 0.2 mM for amiloride and 0.05 mM for hexamethyleneamiloride). Asn was able to double the uptake of 22Na+, whether an ionic (choline chloride) or nonionic (D-mannitol) substance was substituted for Na+, and the substitution of these compounds as well as N-methyl-glucamine for Na+ largely prevented the stimulation of ODC by Asn. Another factor influencing ODC activity was extracellular pH (pHo). When pHo was lowered, intracellular pH (pHi) also fell, and ODC activity was reduced. When pHo was raised, pHi also rose, and ODC activity increased. The well-known correlation between increased pHi and Na+ uptake with the stimulation of growth may be due to their influence on ODC activity.
McCormack
S A
SA
Department of Physiology and Biophysics, University of Tennessee College of Medicine, Memphis 38163.
Tague
L L
LL
Gragoe
E J
EJ
Johnson
L R
LR
D000230:Adenocarcinoma; D000584:Amiloride / Q000494:pharmacology; D001216:Asparagine / Q000494:pharmacology; D002460:Cell Line; D002794:Choline / Q000494:pharmacology; D003110:Colonic Neoplasms; D003470:Culture Media; D004338:Drug Combinations / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D008536:Meglumine / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*
D003470:Culture Media; D004338:Drug Combinations; D008353:Mannitol; D008536:Meglumine; D001216:Asparagine; D000584:Amiloride; D012964:Sodium; D009955:Ornithine Decarboxylase; D002794:Choline