Galactose transport inhibition by cytochalasin E in rat intestine in vitro

Cytochalasins are cytoskeleton disrupters, and cytochalasin E has been repo rted to increase intestinal paracellular permeability. In this study, the c ytochalasin E effect on galactose transport has been investigated. Ussing-t ype chamber experiments show an inhibitory effect of 20 mu M cytochalasin E on unidirectional mucosal to serosal flux of galactose. On the contrary, t he opposite unidirectional flux is not modified by the inhibitor. Results u sing intestinal everted sacs and rings confirm that galactose uptake by the tissue is diminished by cytochalasin E. The effect appears already after 5 min incubation, depends on cytochalasin E concentration, and does not occu r in the absence of Na+. The inhibition is accompanied by an increase in th e apparent K-m of the active sugar transport (11.5 vs.15.8 mM) without sign ificant change in the V-max (10.6 vs. 9.1 mu mol.g(-1) wet weight.5 min(-1) ). Cytochalasin E does not modify either galactose uptake by brush border m embrane vesicles or Na+-K+ ATPase activity in the enterocytes, indicating t hat the inhibitory effect on the Na+-dependent sugar transport cannot be ex plained as a direct effect on SGLT1 activity or as an indirect effect throu gh the Na+-K+ ATPase. Thus, our results suggest that cytochalasin E decreas es SGLT1 activity indirectly through cytoskeleton disruption.