Effect of phenolphthalein on monkey intestinal water and electrolyte transport

Abstract

To assess Na-K-ATPase inhibiton and prostaglandin synthesis stimulation as the mechanism of the secretory (cathartic) action of phenolphthalein in the primate, we investigated water and electrolyte transport and Na-K-ATPase levels in monkey intestine. Both jejunum and colon were studied with in vivo perfusion and in vitro Ussing chamber techniques. Water, Na, and Cl absorption was inhibited or secretion was induced by phenolphthalein (10(-3) M) in the jejunum and colon when the drug was present in the mucosal bathing (perfusion) solution. Serosal addition of phenolphthalein (10(-4) or 10(-3) M) induced Na and anion absorption in the jejunum but not in the colon. Phenolphthalein inhibited Na-K-ATPase activity in the test tube, but assays of intestine previously perfused or bathed in the drug showed no inhibiton. Indomethacin, in doses sufficient to inhibit prostaglandin synthesis in the intestine, inhibited the secretion induced by phenolphthalein in the jejunum but not in the colon. These inconsistencies cast doubt on the role of Na-K-ATPase inhibition or the role of prostaglandin synthesis stimulation in the mechanism of action of phenolphthalein.

Mechanistic bases for differences in passive absorption

“…Indeed, intact pigeons absorbed twice as much Larabinose and L-rhamnose as did intact laboratory rats. Because these molecules presumably permeate across the small intestinal mucosal epithelium primarily through the paracellular pathway (Powell, 1987), and because paracellular transport involves movement of compounds across the size-selective tight junction inbetween intestinal epithelial cells (Powell, 1987), we also expected, and found, that the smaller probe (L-arabinose, M r =150) was absorbed more readily than the larger probe (Lrhamnose, M r =164) in both species.…”

“…We used net water flux as a proxy for determining paracellular net fluid movement, but there is no known direct method to determine the pathway of water movement in the small intestine, and the molecular mechanisms and relative importance of paracellular and transcellular fluid movement are unclear. It is thought that water moves passively across the tight junction or the cell membrane due to osmotic gradients created by solute absorption (Masyuk et al, 2002), but there is only indirect evidence and theories to support transcellular (Loo et al, 1996;Meinild et al, 1998; Ramirez-Lorca et al, 1999; Zeuthen et al, 2001;Zeuthen et al, 1997) or paracellular (Fromter and Diamond, 1972;Pappenheimer and Reiss, 1987;Powell, 1987) modes of fluid transport. In future studies, it would be interesting to compare differential expression of aquaporin isoforms (Ma and Verkman, 1999) between rats and pigeons as well as differences in water flux via SGLT1 (Zeuthen et al, 1997) between mammals and birds.…”

“…Water-soluble molecules, like glucose, are not permeable in the lipid bilayer, thus this membrane is a limiting factor for the absorption of hydrophilic molecules. Unless they are taken up by specialized transporters and moved transcellularly, medium to large hydrophilic molecules presumably permeate across the small intestinal mucosal epithelium primarily through the paracellular pathway (Powell, 1987).…”

Functional characterization and localization of AQP3 in the human colon

“…The opposite can also occur, i.e., the small and large intestine can secrete large amounts of water in the presence of toxins or endogenous secretagogues (2,3). It is generally accepted that these important fluid transfers are associated with salt reabsorption or secretion.…”

Low salt intake down-regulates the guanylin signaling pathway in rat distal colon

“…Frozen tissues were homogenized in HEPES buffer (25 mmol/L pH 7.4) containing a mixture of protease inhibitors, as previously described.15 After assaying protein levels (Bradford assay; BioRad, Richmond, CA), samples containing 40 μg of protein were analyzed by Western blotting using antibodies 2538 (raised against rat preproguanylin [24][25][26][27][28][29][30][31][32][33][34][35][36][37] ) and 6240 (raised against rat preproguanylin 85-99 ). Antibody 6240 was kindly provided by Dr. Sharon Milgram (Chapel Hill, NC).…”