Differences between mechanisms of action of heat-stable and heat-labile enterotoxins of Escherichia coli

Abstract

The mucosal-to-serosal and serosal-to-mucosal fluxes of Na⁺ and Cl^- were measured in control mice and mice treated with heat-stable (ST) and heat-labile (LT) enterotoxins in the presence or absence of: Ca²⁺-ionophore A23187, an activator of Ca²⁺-calmodulin; or phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C9PKC); or 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H-7), an inhibitor of PKC. There was net secretion of Na⁺ and CL^- in both experimental groups in contrast to net absorption in the control group. The addition of ionophore or PMA or ionophore + PMA resulted in net secretion of Na⁺ and Cl^- in the control group and the effect of ionophore and PMA was found to be additive. The addition of ionophore did not cause any change in electrolyte fluxes in the ST toxin treated group, however, it increased the net secretion of Na⁺ and Cl^- in the LT toxin treated group. PMA increased the net secretion of Na⁺ and Cl^- in the ST toxin treated group, however, it did not cause any change in Na⁺ and Cl^- fluxes in the LT toxin treated group. H-7 did not reverse the effect of ST toxin, however, it reversed the effect of LT toxin. These studies suggest that ST toxin acts through the Ca²⁺-calmodulin pathway and secretion of Na⁺ and Cl^- in ST toxin treated mice is due to an increase in the intestinal Ca²⁺-calmodulin activity, whereas, LT toxin acts through the protein kinase C pathway and secretion of Na⁺ and Cl^- in LT toxin treated mice is due to an increase in the intestinal PKC activity.