Role of prostaglandin E2 in contractile abnormality induced by calcium ionophore, A23187.

We evaluated the possible role of prostaglandin E2 (PGE2) in the calcium(Ca++)-mediated damage of skeletal muscle by a calcium ionophore (A23187) that induces excessive Ca++ influx. Twitch and tetanus of rat diaphragms were depressed with either PGE2 or A23187. A23187-induced depression was reduced by PG synthesis inhibitors, aspirin, or indomethacin, though less than that by a protease inhibitor, leupeptin. PGE2-induced depression was also inhibited by leupeptin. Damage of the muscle cell by excessive intracellular free Ca++ may thus be mediated via a PGE2 pathway besides other mechanisms including non-lysosomal, Ca++-activated proteases.