title: PGE1 and prostacyclin suppression of NK-cell mediated cytotoxicity and its relation to cyclic AMP.
abstract: The capacity of three prostanoids (PGE1, 6-beta-PGI1, PGI2 or prostacyclin) and a phosphodiesterase inhibitor (rolipram) to inhibit NK ("natural killer") cell cytotoxicity and to raise cyclic AMP levels in purified NK cells was compared. PGE1 was about 200 times more potent than prostacyclin both in its ability to raise cyclic AMP and to inhibit NK cell cytotoxicity. The stable prostacyclin analogue, 6-beta-PGI1, had an intermediate potency. A 50% inhibition of cytotoxicity was obtained at approximately 10(-8) M for PGE1, 10(-7) M for 6-beta-PGI1, and 10(-6) M for both prostacyclin and rolipram. These doses raised the level of cyclic AMP by approximately 100%. These results suggest that PGE1 is likely to be more important as an endogenous regulator of lymphocyte cytotoxicity than prostacyclin. The results also provide further evidence that cyclic AMP is the mediator of prostanoid-induced reduction in NK cell activity.
mesh_terms: D000527:Alprostadil; D000242:Cyclic AMP / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram
chemical_list: D010726:Phosphodiesterase Inhibitors; D011458:Prostaglandins E; D011760:Pyrrolidinones; C022228:5,6-dihydroprostacyclin; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil; D020889:Rolipram