The effect of harmaline on intestinal sodium transport and on sodium-dependentd-glucose transport in brush-border membrane vesicles from rabbit jejunum

Abstract

Harmaline inhibition of sodium uptake and of sodium-dependent D-glucose transport was investigated using brush-border membrane vesicles from frozen rabbit jejunum. Under sodium-gradient conditions, "initial" D-glucose uptake (20 s) was inhibited by harmaline at concentrations above 0.5 mM, but at lower harmaline concentrations D-glucose uptake was stimulated by 10--15%. When a similar potassium gradient was used, harmaline had no effect. At concentrations up to 2 mM, harmaline did not alter the equilibrium uptake of D-glucose or D-mannitol. After pre-equilibration with sodium (25 mM), G-glucose uptake was inhibited at harmaline concentrations ranging from 0.1 to 2 mM. Sodium (10 mM) uptake was also inhibited by harmaline. Increasing the sodium concentration reduced the inhibitory effect of harmaline on tracer sodium uptake as well as on sodium-dependent D-glucose uptake. Similar to phlorizin, harmaline (1 mM) was able to prevent glucose-induced sodium influx across the brush-border membrane. Sodium uptake into brush-border membrane vesicles seems to be inhibited at lower harmaline concentrations than sodium-dependent D-glucose uptake. At high (2 mM) inhibitor concentrations, however, sodium-dependent glucose uptake is more strongly inhibited than sodium uptake. These results suggest that harmaline inhibits both sodium and sodium-dependent transport across intestinal brush-border membranes by interacting with specific sodium-binding sites.

Binding of Organic Cations to Brush Border Membrane from Rat Small Intestine

“…Moreover, it was shown by Elsenhans et al (1985) that some organic cations could interfere with Na-dependent transport functions of the small intestinal brush border membrane but did not affect the passive and the facilitated diffusion. One possible reason for the interference might be competitive binding of organic cations to sodium ion binding sites of the active transport system as suggested for harmaline (Alvarado et al 1979). The binding to low-affinity sites may be due to the nonionic interaction in the hydrophobic region of the membrane bilayer as suggested by Kubo et a1 (1986).…”

K+-Dependent Composite Gating of the Yeast K+ Channel, Tok1

“…Both this ⌬ K ϩ dependence and the rapid nature of the R-O transition raised doubt as to whether it reflected the activity of a deactivation gating mechanism akin to those of other Shaker-like channels. Where determined, activation rates of these channels, even the extremely rapid ones, have large temperature dependencies with Q 10 values between 2 and 4 (Beam and Donaldson, 1983;Collins and Rojas, 1982;Alvarado et al, 1979;Chiu et al, 1979;Schauf, 1973;Moore, 1971;Dudel and Rudel, 1970;Frankenhauser and Moore, 1963;Hodgkin and Katz, 1949), reflecting sizable enthalpic barriers between the open and closed states, indicating a substantial conformational transition. Because the activation rate from the R state could be discerned, its temperature dependence could be assessed.…”

Amiloride inhibition of the Na+-H+ exchanger in renal microvillus membrane vesicles

“…with those of harmaline, the only other Na+-H+-exchange inhibitor reported to date (2,4 (5). Accordingly, amiloride may be most useful as a selective inhibitor of Na+-H' exchange when it is employed in the presence of lower than normal Na' concentrations.…”