Pharmacology of functional endogenous IP prostanoid receptors in NCB-20 cells: comparison with binding data from human platelets

• Published in: Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2001-11, Vol.65 (5-6), p.253-258
• Main Authors: Crider, J.Y., Xu, S.X., Sharif, N.A.
• Format: Article
• Language: English
• Subjects: Alprostadil - analogs & derivatives; Alprostadil - metabolism; Alprostadil - pharmacology; Animals; Biological and medical sciences; Blood Platelets - metabolism; Cyclic AMP - metabolism; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Dinoprost - pharmacology; Dinoprostone - metabolism; Dinoprostone - pharmacology; Humans; Iloprost - metabolism; Iloprost - pharmacology; Mice; Misoprostol - metabolism; Misoprostol - pharmacology; Neuroblastoma - metabolism; Radioimmunoassay; Receptors, Epoprostenol; Receptors, Prostaglandin - agonists; Receptors, Prostaglandin - drug effects; Receptors, Prostaglandin - metabolism; Tumor Cells, Cultured
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1054/plef.2001.0322

The objective of these studies was to characterize the effects of a broad range of prostanoid agonists upon the stimulation of cAMP production in National Cancer Bank (NCB-20; mouse neuroblastoma/hamster brain hybridoma) cells. The pharmacology of these functional responses in NCB-20 cells was compared with that of the classic endogenous IP receptor present on human platelets using [3H]-iloprost binding techniques. In both assay systems, agonists from the IP prostanoid class exhibited the highest affinities and functional potencies. Specific prostanoids exhibited the following rank order of potency (EC50±SEM) in stimulating cAMP production in the NCB-20 cells: carbaprostacyclin (4.3±0.9 nM) = PGI2 (6.6±1.5 nM) > iloprost (75±13 nM)> 11-deoxy PGE1 (378±138 nM) > misoprostol (1243±48) > PGE2 (3020±700 nM) > ZK-118182 (7265±455 nM). Iloprost was the most potent compound in the human platelet binding assay while prostanoids from the DP and EP receptor classes showed modest affinity. These studies provide functional and binding information for a broad range of both natural and synthetic prostanoid receptor ligands at the endogenous IP receptor in two different cell types.