Studies on chemical mediator release from guinea pig lung fragments by Ca ionophore, A23187 (Π)

A Ca ionophore, A23187 has been thought to induce the chemical mediator release from a variety of cells by directly transporting Ca++ into the related cells. Our previous experiments on the release of histamine and slow reacting substance(SRS) from guinea pig lung fragments have suggested that A23187 activates cells prior to Ca++ influx for the release. In this report, we further examined the mode of action of A23187 in the release. The results obtained were as follows: 1) The release of histamine and SRS by A23187 was gradually increased with incubation time, reaching the maximum at 60 to 100min, as previously reported(whole stage). Under the same conditions without Ca++ & Mg++(lst stage), a small amount of both mediators was detected. 2) After 60min incubation at the 1st stage, an addition of Ca++(2nd stage) followed by 40min incubation induced the marked release of both mediators, but Mg++ did not lead to the release. The release by an addition of Ca++ at the 2nd stage was clearly different from that of the whole stage in terms of the very rapid and marked(1.5-fold in histamine & 2-fold in SRS at the whole stage) release. 3) An addition of bovine serum albumin which effectively binds with A23187, during the whole stage, caused surplus histamine and SRS release. 4) Both histamine and SRS release were dose-dependently inhibited by the treatment with diisopropyl-fluorophosphate. From the above results, it was further suggested that A23187 activates the cells prior to Ca++ influx.