The effect of phenolphthalein on rabbit ileal electrolyte transport was studied to gain insight into the mechanism of cathartic action of this drug. Two separate effects were noted in Ringer solution in the Ussing chamber in vitro. First, when present in either or both the mucosal and serosal solutions, phenolphthalein caused a dose-related inhibition of the potential difference and the short-circuit current. Second, when present only on the mucosal side of the epithelium, phenolphthalein inhibited sodium chloride absorption (or caused sodium chloride secretion); when present only on the serosal side, phenolphthalein stimulated sodium chloride absorption. There was no clear difference between the effects of white and yellow phenolphthalein. In sodium-free solutions, mucosal phenolphthalein inhibited an apparent chloride:bicarbonate exchange, in chloridefree, bicarbonate-free, and chloride-bicarbonate-free solutions, mucosal phenolphthalein inhibited sodium absorption, while serosal phenolphthalein stimulated sodium absorption, as it did in Ringer solution. However, the ion accompanying the change in sodium transport in these anion-substituted solutions was the residual flux (? bicarbonate or hydrogen ion). At 10-4 M, mucosal phenolphthalein but not serosal phenolphthalein inhibited glucose- and alanine-stimulated short-circuit current. Phenolphthalein did not increase tissue levels of cyclic nucleotides. Luminal phenolphthalein initially caused secretion in vivo, but this was short lived, perhaps indicating a serosal absorptive effect of the drug as it was transported across the epithelium. The inhibitory effects of mucosal phenolphthalein can be explained by inhibition of sodium-potassium adenosine triphosphatase and by inhibition of anion exchange and possibly sodium-coupled (chloride, glucose, and alanine) transport processes. The mechanism of the absorptive action of serosal phenolphthalein remains to be elucidated. It is clear, however, that this drug affects intestinal electrolyte transport by mechanisms other than inhibition of the sodium pump or by stimulating secretion via cyclic nucleotides.
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