Phenolphthalein- and harmaline-induced disturbances in the transport functions of isolated brush border and basolateral membrane vesicles from rat jejunum and kidney cortex

Phenolphthalein and harmaline were examined with respect to their effects on the transport functions of purified brush border and basolateral membrane vesicles from rat jejunum and kidney cortex. Phenolphthalein (0.5 mM) inhibited Na⁺-coupled d-glucose uptake by intestinal brush border membrane vesicles without affecting Na⁺-coupled l-alanine transport, Na⁺ transport or Na⁺-independent d-glucose transport. In renal brush border membrane vesicles, the same concentration of this drug did not even affect Na⁺-coupled d-glucose uptake. At a concentration of 1 mM or higher, however, Phenolphthalein rendered both intestinal and renal vesicles leaky to these solutes. In intestinal and renal basolateral membrane vesicles, phenolphthalein at a concentration of 0.5 mM noticeably inhibited (Na⁺-K⁺)-ATPase activity, but showed no effect on phloretin-sensitive Na⁺-independent d-glucose uptake. At 1 mM this drug also inhibited ouabain-insensitive ATPase activity. Harmaline, at concentrations greater than 2 mM, inhibited not only Na⁺-coupled d-glucose and l-alanine uptake by both intestinal and renal brush border membrane vesicles, but also Na⁺ translocation. The drug, however, affected neither Na⁺-independent d-glucose uptake nor the general permeability of these membranes. Harmaline also inhibited (Na⁺-K⁺)-ATPase activity of intestinal and renal basolateral membrane vesicles without affecting ouabain-insensitive ATPase. It did not influence, however, phloretin-sensitive Na⁺-independent d-glucose uptake by these vesicles. These observations suggest that harmaline acts as an inhibitor of Na⁺ and Na⁺-dependent transport mechanisms in intestinal as well as renal brush border membranes. Phenolphthalein at the lower concentration selectively inhibited certain transport processes in these membranes as well as in basolateral membranes, whereas at the higher concentration it caused widespread structural disturbances, possibly through its chaotropic action on membranes.