Pharmacology of functional endogenous IP prostanoid receptors in NCB-20 cells: comparison with binding data from human platelets.
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 PGE, (378+/-138 nM) > misoprostol (1,243+/-48) > PGE2 (3020+/-700 nM) > ZK-118182 (7265+/-455 nM). Iloprost wasthe most potent compound in the human platelet binding assay while prostanoidsfromthe DPand 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.
Crider
J Y
JY
Molecular Pharmacology Unit, Alcon Research, Ltd, Forth Worth, TX 76134-2099, USA. julie.crider@alconlabs.com
Xu
S X
SX
Sharif
N A
NA
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D016595:Misoprostol / Q000378:metabolism / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D011863:Radioimmunoassay; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C113936:PTGIR protein, human; C491910:Ptgir protein, mouse; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D016595:Misoprostol; C067426:ZK 118182; D015237:Dinoprost; D000242:Cyclic AMP; D000527:Alprostadil; D016285:Iloprost; D015232:Dinoprostone; C034008:11-deoxyprostaglandin E1