Effects of calcium and A23187 on renal inner medullary prostaglandin E2 synthesis

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Abstract
The mechanism of the Ca2+-inophore A23187[2-[(3.beta.,9.alpha.,11.beta.-trimethyl)-8-(2-pyrrole carboxymethyl)-1,7-dioxaspiro[6.6]undecyl-2.beta.-methyl]-5-methylamino benzoxazole-4-carboxylic acid]-mediated increase in prostaglandin(PG)E2 synthesis by [rat] inner medullary slices was examined. Slices were prelabeled with [1-14C]arachidonic acid prior to addition of Ca2+ and ionophore. The effects of Ca2+ and A23187 were evaluated by analysis of total radioactivity, [14C]arachidonic acid and [14C]PGE2 in media. Media contents of [14C]arachidonic acid and [14C]PGE2 were quantitated by TLC. Ca when added with A23187 caused an increase in the media content of total radioactivity, [14C]arachidonic acid and [14C]PGE2. Ca2+, Mg2+, ionophore or ionophore and Mg2+ were without effect. Indomethacin completely blocked [14C]PGE2 synthesis in control and Ca2+-ionophore-treated slices and increased media [14C]arachidonic acid. The total amount of radioactivity in the media was not altered. With indomethacin, the increase in [14C]arachidonic acid observed apparently was due to reduced conversion of the [14C]arachidonic acid to [14C]PGE2 by PG cyclooxygenase. Slices prelabeled with [14C]palmitic acid did not demonstrate a Ca-ionophore-mediated increase in total media radioactivity. Ca2+-ionophore apparently mediates a selective accumulation of media arachidonic acid compared to palmitic acid. Ca2+-ionophore apparently increased PGE2 synthesis by increasing the available substrate (arachidonic acid) for PG cyclooxygenase. Arachidonic acid availability may be a rate-determining step in PG synthesis.