The inhibition of the serum-stimulated increase of ornithine decarboxylase by ionophores and local anesthetics.
The addition of fresh serum-containing growth medium to L1210 mouse leukemic cells in culture resulted in a 5-fold increase in ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity. The presence of microtubule disrupting agents (colchicine, vinblastine) or cations (5-10 mM K+, Na+ or Mg2+) abolishes this increase of ornithine decarboxylase activity. (Chen, K.Y., Heller, J.S. and Canellakis, E.S. (1976) Biochem. Biophys. Res. Commun. 70, 212-219). Based on these observations we proposed that fluctuation in cellular cation concentrations may act as a link between the membrane structure and ornithine decarboxylase. To test this proposal, we studied the effects of selective membrane perturbing agents such as ionophores and local anesthetics, on the serum-stimulated increase of ornithine decarboxylase activity in L1210 cells. Among the six ionophores tested, valinomycin was the most potent one, with I50 value (concentration that gives 50% inhibition of ornithine decarboxylase activity) of 6.10(-9) M. Dibucaine and tetracaine were also effective inhibitors at 10(-4)-10(-5) M. The I50 values of valinomycin on the protein synthesis and RNA synthesis, however, were greater than 1.10(-6) M. These results substantiate the notion that ornithine decarboxylase activity can be regulated at plasma membrane level and such regulation is related to the perturbation of cellular cation pools.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001769:Blood; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D003470:Culture Media; D003992:Dibucaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007476:Ionophores / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000201:enzymology; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology; D065108:Ornithine Decarboxylase Inhibitors; D013748:Tetracaine / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D000779:Anesthetics, Local; D003470:Culture Media; D007476:Ionophores; D065108:Ornithine Decarboxylase Inhibitors; D013748:Tetracaine; D014634:Valinomycin; D002262:Carboxy-Lyases; D003992:Dibucaine