Role of Ca2(+)-calmodulin and protein kinase C in the secretory action of heat-labile enterotoxin of Escherichia coli in mice.

The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were carried out in control and heat-labile enterotoxin treated mice in the presence or absence of Ca2(+)-ionophore A23187, the activator of Ca2(+)-calmodulin or Phorbol-12-myristate-13-acetate (PMA), the activator of Protein kinase C (PKC) or 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H-7), an inhibitor of PKC. There was net secretion of Na+ and Cl- in experimental group in comparison to net absorption in control group. The addition of ionophore or PMA resulted in net secretion of Na+ and Cl- in control group. In experimental group ionophore increased the net secretion of Na+ and Cl- while, PMA could not cause any change in Na+ and Cl- fluxes in experimental group. Calmodulin activity remained unaltered in heat-labile enterotoxin treated mice as compared to control. H-7, reversed the effects of PMA and heat-labile enterotoxin. These studies demonstrate that heat-labile enterotoxin primarily involves PKC in its action.