An EP receptor with a novel pharmacological profile in the T-cell line Jurkat

1. Comparison of the rank order of potency of the natural prostanoids prostaglandin E2 (PGE2), PGD2, PGF2 alpha and carbaprostacyclin in stimulating cyclic AMP in Jurkat cells is consistent with the presence of an EP receptor. 2. Lack of responsiveness to the EP1/EP3 selective agonist, sulprostone, and the EP2 agonists, butaprost and AH 13205, indicates that this receptor is not of the EP1, EP2 or EP3 subtypes. 3. Inhibition of PGE2-stimulated cyclic AMP by the EP4 antagonist, AH 23848 is non-competitive, unlike the competitive antagonism reported in the pig saphenous vein EP4 preparation. Furthermore, 16,16-dimethyl PGE2 is 100 fold less potent than PGE2 in Jurkat cells, while these agonists are equipotent in the rabbit jugular vein purported EP4 preparation. In addition, 1-OH PGE1, which also is active in the rabbit jugular vein preparation, is inactive in Jurkat cells at concentrations up to 1 x 10(-4) M. These data are not wholly consistent with any adenylate cyclase coupled EP receptor described to date. 4. It is postulated that an EP receptor, positively coupled to adenylate cyclase, with a unique pharmacological profile is present in Jurkat cells.