The effect of microtubular inhibitors on transport of α-aminoisobutyric acid. Inhibition of uphill transport without changes in transmembrane gradients of Na+, K+, or H+

I. David Goldman, Mary Jo Fyfe, Donnell Bowen, Sharon Loftfield, James A. Schafer

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A prior study indicated that vinca alkaloids partially inhibit the uphill transport of α-aminoisobutyric acid in Ehrlich ascites tumor cells. Maximum inhibition reduced the steady-state α-aminoisobutyric acid distribution ratio by only 25% leaving a large residual gradient. Studies were undertaken in two independent laboratories to correlate alterations in α-aminoisobutyric acid transport induced by vinca alkaloids with electrochemical potential differences for Na+, K+, or H+ across the cell membrane. Vincristine reduced the transmembrane steady-state gradient for α-aminoisobutyric acid by 13% (Richmond) or 18% (Alabama), respectively. Vinblastine reduced this gradient by 14.5%. There was no concurrent change in the chemical gradients for Na+, K+, or H+ across the cell membrane. A small, 4.08%, increase in the Cl- distribution ratio would not account for the much larger change in α-aminoisobutyric acid gradients on the basis of a decrease in the electrochemical potential for intracellular Na+. These data indicate that the decrease in the α-aminoisobutyric acid gradient across the Ehrlich ascites tumor cell membrane induced by vinca alkaloids cannot be attributed to a fall in the transmembrane electrochemical potential differences for Na+, K+, or H+. The data suggest a role for cellular microtubules in the uphill transport of α-aminoisobutyric acid in this cell system.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalBBA - Biomembranes
Volume467
Issue number2
DOIs
StatePublished - Jun 2 1977
Externally publishedYes

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Aminoisobutyric Acids
Active Biological Transport
Vinca Alkaloids
Cell membranes
Ehrlich Tumor Carcinoma
Cell Membrane
Tumors
Vinblastine
Vincristine
Microtubules
Membrane Potentials
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Medicine(all)

Cite this

The effect of microtubular inhibitors on transport of α-aminoisobutyric acid. Inhibition of uphill transport without changes in transmembrane gradients of Na+, K+, or H+. / Goldman, I. David; Fyfe, Mary Jo; Bowen, Donnell; Loftfield, Sharon; Schafer, James A.

In: BBA - Biomembranes, Vol. 467, No. 2, 02.06.1977, p. 185-191.

Research output: Contribution to journalArticle

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abstract = "A prior study indicated that vinca alkaloids partially inhibit the uphill transport of α-aminoisobutyric acid in Ehrlich ascites tumor cells. Maximum inhibition reduced the steady-state α-aminoisobutyric acid distribution ratio by only 25{\%} leaving a large residual gradient. Studies were undertaken in two independent laboratories to correlate alterations in α-aminoisobutyric acid transport induced by vinca alkaloids with electrochemical potential differences for Na+, K+, or H+ across the cell membrane. Vincristine reduced the transmembrane steady-state gradient for α-aminoisobutyric acid by 13{\%} (Richmond) or 18{\%} (Alabama), respectively. Vinblastine reduced this gradient by 14.5{\%}. There was no concurrent change in the chemical gradients for Na+, K+, or H+ across the cell membrane. A small, 4.08{\%}, increase in the Cl- distribution ratio would not account for the much larger change in α-aminoisobutyric acid gradients on the basis of a decrease in the electrochemical potential for intracellular Na+. These data indicate that the decrease in the α-aminoisobutyric acid gradient across the Ehrlich ascites tumor cell membrane induced by vinca alkaloids cannot be attributed to a fall in the transmembrane electrochemical potential differences for Na+, K+, or H+. The data suggest a role for cellular microtubules in the uphill transport of α-aminoisobutyric acid in this cell system.",
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