Prostanoid receptor with a novel pharmacological profile in human erythroleukemia cells.
The purpose of this study was to characterize the prostanoid receptors coupled to intracellular calcium in human erythroleukemia (HEL) cells, a cell line with platelet/megakaryocytic characteristics. Both prostaglandin E1 (PGE1) and iloprost increased cyclic AMP (cAMP) in HEL cells, but modulated [Ca2+]i by different mechanisms. Iloprost (10(-9) to 10(-6) M) had no effect on basal [Ca2+]i, but greatly potentiated the increase in [Ca2+]i produced by thrombin. This effect was mimicked by cholera toxin and other Gs-coupled receptors, and involved calcium influx since iloprost had no effect on [Ca2+]i in cells incubated in Ca2+-free buffer. Furthermore, iloprost did not increase the generation of baseline or thrombin-induced inositol phosphates at these concentrations. In contrast, PGE1 (10(-7) to 10(-5) M), but not iloprost, increased basal [Ca2+]i through a pertussis toxin-sensitive mechanism that involved stimulation of inositol phosphate generation and mobilization of intracellular calcium. The order of potencies of other prostaglandins that increased [Ca2+]i was not consistent with known IP, EP, DP, FP, or TP receptors. 11-Deoxy-16,16-dimethyl PGE2 was the most potent of the analogs tested (EC50 = 28 nM). In summary, at least two prostaglandin receptors are functionally coupled to intracellular calcium in HEL cells: a putative IP receptor coupled to Gs proteins that increases cAMP and enhances calcium influx, and a novel prostanoid receptor that evokes calcium mobilization through stimulation of phospholipase C by a pertussis toxin-sensitive pathway.
Feoktistov
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Department of Medicine, Vanderbilt University, Nashville, TN 32732-2195, U.S.A.
Breyer
R M
RM
Biaggioni
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D015064:16,16-Dimethylprostaglandin E2 / Q000031:analogs & derivatives / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D013917:Thrombin; D000527:Alprostadil; D016285:Iloprost; D015064:16,16-Dimethylprostaglandin E2; D002118:Calcium