A reduction in energy dependent amino acid transport by microtubular inhibitors in Ehrlich ascites tumor cells

M. J. Fyfe, S. Loftfield, I. David Goldman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Vincristine, other periwinkle alkaloids, and colchicine partially inhibit the energy dependent transport of α aminoisobutyric acid in Ehrlich ascites tumor cells. The properties of this phenomenon were characterized in detail for vincristine. Maximum depression of the steady state intracellular α aminoisobutyric acid level was achieved with a vincristine concentration of <0.5 μM. The inhibitory effect of vincristine increases as the extracellular α aminoisobutyric acid concentration is increased reaching a maximum, however, of only 25% at a level of 5 mM, leaving a large gradient for α aminoisobutyric acid across the cell membrane. Vincristine produced an asymmetrical effect on the bidirectional fluxes decreasing the initial uptake rate, while increasing the efflux of α aminoisobutyric acid. Inhibition of net α aminoisobutyric acid transport by vincristine was partially reversible (40%). Colchicine (50 μM) reduced the steady state α aminoisobutyric acid level by 30%, an effect that was not reversible. Inhibition by vinleurosine and vinrosidine was comparable to that of vincristine. Addition of glucose to the medium resulted in a small, but significant, decrease in the inhibitory effects of both vincristine and colchicine. The data indicate that these agents inhibit a small component of the uphill transport of α aminoisobutyric acid in Ehrlich ascites tumor cells. The inhibitory effect of vincristine cannot be attributed to an increase in the passive permeability of the cell membrane to this agent. Rather, the data along with other studies from this laboratory suggest that vincristine reduces the energy dependent transport of α aminoisobutyric acid by either inhibiting cellular energy metabolism or by inhibiting the coupling of energy metabolism to the transport of this amino acid and they raise the possibility that cellular microtubules play a role in these processes.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
Volume86
Issue number2
StatePublished - 1975
Externally publishedYes

Fingerprint

Ehrlich Tumor Carcinoma
Aminoisobutyric Acids
Vincristine
Tumors
Cells
Amino Acids
Colchicine
Cell membranes
Energy Metabolism
Vinca
Cell Membrane Permeability
Active Biological Transport
Alkaloids
Microtubules
Cell Membrane
Fluxes
Glucose

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

A reduction in energy dependent amino acid transport by microtubular inhibitors in Ehrlich ascites tumor cells. / Fyfe, M. J.; Loftfield, S.; Goldman, I. David.

In: Journal of Cellular Physiology, Vol. 86, No. 2, 1975.

Research output: Contribution to journalArticle

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abstract = "Vincristine, other periwinkle alkaloids, and colchicine partially inhibit the energy dependent transport of α aminoisobutyric acid in Ehrlich ascites tumor cells. The properties of this phenomenon were characterized in detail for vincristine. Maximum depression of the steady state intracellular α aminoisobutyric acid level was achieved with a vincristine concentration of <0.5 μM. The inhibitory effect of vincristine increases as the extracellular α aminoisobutyric acid concentration is increased reaching a maximum, however, of only 25{\%} at a level of 5 mM, leaving a large gradient for α aminoisobutyric acid across the cell membrane. Vincristine produced an asymmetrical effect on the bidirectional fluxes decreasing the initial uptake rate, while increasing the efflux of α aminoisobutyric acid. Inhibition of net α aminoisobutyric acid transport by vincristine was partially reversible (40{\%}). Colchicine (50 μM) reduced the steady state α aminoisobutyric acid level by 30{\%}, an effect that was not reversible. Inhibition by vinleurosine and vinrosidine was comparable to that of vincristine. Addition of glucose to the medium resulted in a small, but significant, decrease in the inhibitory effects of both vincristine and colchicine. The data indicate that these agents inhibit a small component of the uphill transport of α aminoisobutyric acid in Ehrlich ascites tumor cells. The inhibitory effect of vincristine cannot be attributed to an increase in the passive permeability of the cell membrane to this agent. Rather, the data along with other studies from this laboratory suggest that vincristine reduces the energy dependent transport of α aminoisobutyric acid by either inhibiting cellular energy metabolism or by inhibiting the coupling of energy metabolism to the transport of this amino acid and they raise the possibility that cellular microtubules play a role in these processes.",
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