The mechanism of action of Senokot, a widely used laxative, has not been established. Senokot was given orally to rats 8-14 h before intestinal water and electrolyte transport were studied. Senokot significantly decreased colonic and jejunal water absorption measured in vivo by the single-pass perfusion technique. The Senokot changes were not associated with changes in jejunal or colonic histology or adenylate cyclase activity or colonic cyclic adenosine monophosphate content. Senokot also altered active electrolyte transport in rat descending colon as measured by the Ussing chamber-voltage clamp technique. These changes consisted of an increase in short-circuit current and a decrease in active Na and Cl transport that was due to a decrease in the mucosal-to-serosal fluxes. The changes in active electrolyte transport were dependent on Ca++ in the serosal but not the mucosal bathing solution. In contrast, addition of 10(-4) M verapamil to the serosal surface did not alter the Senokot effect. In spite of a dependence on serosal Ca++, Senokot did not alter 45Ca++ entry across the colonic serosal surface. The phospholipase A2 inhibitor quinacrine (10(-4) M) also did not alter the effect of Senokot on colonic Na and Cl transport. Senokot alters active colonic Na and Cl transport via a presently unknown mechanism that is dependent on serosal Ca++.
Adenylyl Cyclases Animals