Functional pharmacology of human prostanoid EP2 and EP4 receptors
| Autor: | David W. Gray, Richard L. Wood, Heather Giles, Vanessa J. Shield, L. Staton Noel, Richard J. Wilson, Sharron A. Rhodes |
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| Rok vydání: | 2004 |
| Předmět: |
Pharmacology
Agonist Dose-Response Relationship Drug medicine.drug_class Prostaglandin E2 receptor Prostanoid Prostaglandin Receptors Prostaglandin E EP2 Subtype Partial agonist Cell Line chemistry.chemical_compound chemistry Cyclic AMP Prostaglandins medicine Humans Receptors Prostaglandin E lipids (amino acids peptides and proteins) Prostaglandin D2 Prostaglandin E2 Receptor Receptors Prostaglandin E EP4 Subtype medicine.drug |
| Zdroj: | European Journal of Pharmacology. 501:49-58 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2004.08.025 |
| Popis: | Prostanoid EP(2) and EP(4) receptor-mediated responses are difficult to distinguish pharmacologically because of the lack of potent, selective antagonists. We describe systematic agonist fingerprints for recombinant human prostanoid EP(2) and EP(4) receptors expressed in CHO and HEK293 cells, respectively. The rank orders of potency of endogenous prostaglandins were: prostanoid EP(2) receptors: prostaglandin E(2)prostaglandin D(2)=prostaglandin F(2alpha)prostaglandin I(2); prostanoid EP(4) receptors: prostaglandin E(2)prostaglandin I(2)prostaglandin D(2)=prostaglandin F(2alpha). Butaprost free acid (9-oxo-11alpha,16R-dihydroxy-17-cyclobutyl-prost-13E-en-1-oic acid) behaved as a highly selective partial agonist at prostanoid EP(2) receptors while butaprost methyl ester elicited small, low potency responses. The prostanoid EP(1) and EP(3) receptor agonists misoprostol (9-oxo-11alpha,16-dihydroxy-16-methyl-prost-13E-en-1-oic acid, methyl ester), sulprostone (N-(methylsulphonyl)-9-oxo-11alpha,15R-dihydroxy-16-phenoxy-17,18,19,20-tetranor-prosta-5Z,13E-dien-1-amide), and GR63799X ([1R-[1alpha(Z),2beta(R*),3alpha]-(-)-4-benzoylamino)phenyl-7-[3-hydroxy-3-phenoxy-propoxy)-5-oxocyclopentyl]-4-heptenoate), and the prostanoid DP receptor agonist BW245C ((4S)-(3-[(3R,S)-3-cyclohexyl-3-hydropropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid), activated both prostanoid EP(2) and EP(4) receptors. Prostaglandin I(2), iloprost (6,9alpha-methylene-11alpha,15S-dihydroxy-16-methyl-prosta-5E,13E-dien-18-yn-1-oic acid, trometamol salt) and cicaprost (5-[(E)-(1S, 5S, 6S, 7R)-7-hydroxy-6-[(3S, 4S)-3-hydroxy-4-methylnona-1,6-diinyl]-bicyclo[3.3.0]octan-3-yliden]-3-oxapentanoic acid; ZK96480) were full agonists at prostanoid EP(4) receptors. Key differentiating agonists are: butaprost FA, 16,16-dimethyl-prostaglandin E(2), 19-(R)-hydroxy prostaglandin E(2), misoprostol, BW245C, prostaglandin F(2alpha) and prostaglandin D(2). |
| Databáze: | OpenAIRE |
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