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 arachidonic 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 arachidonate 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.