Inhibition of active sodium transport by cytochalasin B in rat jejunum in vitro

Abstract

The effects of cytochalasin B on electrophysiological properties and sodium transport in rat jejunum in vitro are described. Stripped paired rat jejunal segments were maintained in Ussing chambers with Leibovitz's (L-15) tissue culture medium bubbled with 100% oxygen. L-15 medium contains galactose as the only sugar, and an assortment of amino acids and cofactors to nourish the tissue. Electrophysiological parameters of short-circuit current ( I sc) and transepithelial potential difference could be maintained for up to 4 h in control tissues. Upon application of cytochalasin B (20 μg/ml), on the mucosal side, I sc and potential difference fell within 1 h from 1.93 ± 0.12 to 1.09 ± 0.14 (mean ± S.E.) μequiv./cm 2 per h and from 5 to 2.5 mV. Tissue resistance remained unchanged at approx. 110 Ω·cm 2 for up to 4 h. 22Na net flux was 4.1 ± 0.9 μequiv./cm 2 per h during the last control period and fell to zero within 1 h after cytochalasin B treatment. Transmission electron micrographs revealed no gross morphological changes at this dose. Absorptive junctional morphology was apparently not altered by cytochalasin B treatment, a finding which was consistent with the stable transepithelial electrical resistance observed during exposure to this drug. Active sodium transport processes coupled to hexose, amino acid, and chloride movements are all possible in L-15 medium. However, following exposure to 20 μg/ml cytochalasin B, all net sodium transport is completely inhibited. The data are consistent with the hypothesis of a common regulator for active sodium transport processes which is modulated through structural changes in cytoskeletal organization.