The present work brings the first evidence for the simultaneous release of Paf-acether (platelet-activating factor), slow-reacting substance (SRS), histamine, and serotonin from isolated rat kidneys stimulated with ionophore A 23187. However, with compound 48/80 we detected only SRS, histamine, and serotonin. Upon addition of antigen, kidneys from sensitized rats released Paf-acether and SRS of anaphylaxis. Paf-acether released in the perfusate was identified by its ability to aggregate aspirin-treated washed rabbit platelets in the presence of an ADP scavenger complex. It was also characterized by its inactivation by phospholipase A2, and it was eluted from high pressure liquid chromatography (HPLC) after 16 to 18 min, a retention identical to that of synthetic Paf-acether, that is, between sphingomyelin and lysophosphatidylcholine. The biological activity of SRS was detected after several purification steps including Amberlite XAD-2 and reverse phase HPLC (RP-HPLC). Kidney SRS exhibited a typical spasmogenic activity in isolated guinea-pig ileum preparation that was reversed by FPL 55712. When kidneys were incubated with [3H]arachidonic acid, radioactivity and biological activity comigrated in RP-HPLC with leukotrienes C and D. These results indicate that the kidney is capable of actively released inflammatory mediators.

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