A23187-induced changes in colonic K and Cl transport are mediated by separate mechanisms

Stripped rabbit colonic mucosa was studied in vitro in Ussing chambers to determine 1) effects of the divalent cation ionophore A23187 on K and Cl fluxes and electrical properties; 2) effects of the prostaglandin (PG) synthesis inhibitor indomethacin on A23187-, PGE₁-, and arachidonate acid-induced changes in electrical parameters and K and Cl fluxes; and 3) changes in PGE₂ release in response to A23187, arachidonic acid, indomethacin, or indomethacin and either A23187 or arachidonic acid. Results from these studies demonstrate that A23187, PGE₁, and arachidonic increase net K and Cl secretion. Results with indomethacin reveal that this agent abolishes the increase in Cl secretion stimulated by A23187 or arachidonate but not by PGE₁. Indomethacin also abolished net K secretion stimulated by arachidonate but not by A23187 or PGE₁. These results together with the finding that A23187 like arachidonate increases PGE₂ release in the absence but not the presence of indomethacin suggest that A23187-stimulated Cl secretion occurs by a PG-dependent mechanism, while A23187-induced K secretion occurs by an alternate Ca-dependent mechanism.