Effect of harmaline on rat intestinal brush border sucrase activity

Abstract

The effect of harmaline, a plant alkaloid has been studied on rat intestinal brush border sucrase activity. Stimulation of sucrase activity by Na+ was found to be <i>p</i>H-dependent. At neutral <i>p</i>H<i>, </i>20 m<i>M</i> Na⁺ stimulated sucrase activity by reducing <i>K</i>_m<i> </i>by 30%<i> </i>while at acidic <i>p</i>H<i> </i>(5.2), the activity increased 4-fold compared to Na⁺-free enzyme. At 1.0 m<i>M</i>, harmaline

markedly inhibited (67%)<i> </i>the enzyme activity at <i>p</i>H<i> </i>5.2 in the absence of Na⁺. However, inhibition was reduced in presence of 20 m<i>M</i> sodium, whereas 4.0 m<i>M</i> harmaline was required to inhibit the enzyme activity by 65%<i>. </i>In the absence of Na⁺ ions, harmaline inhibition of sucrase activity was of competitive type, but it changed to non-competitive type in presence of 20<i> m</i>M<i> </i>Na⁺ at <i>p</i>H<i> </i>5.2. Sucrase-harmaline interactions as a function of <i>p</i>H<i>, </i>both in presence and absence of Na⁺ revealed a shift in <i>p</i>H<i> </i>optima of the enzyme towards a higher <i>p</i>H<i> </i>in presence of 4 m<i>M</i> and 1 m<i>M</i> harmaline respectively. The observed inhibition was reversible in nature and was only partially overcome by sodium, lithium, potassium, cesium, rubidium and ammonium ions. These findings suggest that harmaline also inhibits rat brush border sucrase and that the presence of Na⁺ site is not a pre-requisite for the inhibition.