Colonic potassium and chloride secretion: Role of cAMP and calcium

Stripped rabbit colonic mucosa was studied in vitro in Ussing chambers to further investigate the role of Ca in regulating K and Cl secretion stimulated by the divalent cation ionophore A23187, prostaglandin E₁ (PGE₂), or 8-bromo-cAMP (8BrcAMP). To assess the effects of these secretagogues on the paracellular shunt permeability, we measured the Na concentration dependence of the serosal-to-mucosal Na flux in the absence or presence of these stimuli. Results from these studies reveal that changes in net K and Cl secretion produced by secretory stimuli cannot be accounted for by a change in shunt permeability. The possible involvement of Ca in the secretory response of the colon to these stimuli was investigated by measuring the changes in Cl and K transport elicited by A23187, PGE₁, or 8BrcAMP in the absence or presence of trifluoperazine (10^-4 M) added to the serosal bathing solution. Trifluoperazine alone did not significantly alter basal Na or Cl fluxes or short-circuit current (I(sc)) but did decrease transepithelial conductance (G(t)) and the serosal-to-mucosal K flux. Pretreatment of the tissues with trifluoperazine significantly reduced or abolished the changes in K fluxes elicited by A23187, 8BrcAMP, or PGE₁ without altering the changes in Cl transport, I(sc), and G(t). These results suggest that K secretion induced by these secretagogues involves an increase in intracellular Ca concentration and may be mediated by calmodulin.