title: Binding affinities of isocarbacyclin methyl ester and its free acid to prostanoid receptors.
abstract: The binding affinities of isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) and its free acid (CAS 88911-35-7, TEI-7165) to prostaglandin (PG) I2 receptors (IP receptors), PGE2 receptors (EP receptors) and thromboxane A2 receptors (TP receptors) were investigated. TEI-9090 exhibited low affinity for IP and EP receptors in mastocytoma P-815 cell membranes and no affinity for TP receptors in washed guinea-pig platelets. The IC50 values of TEI-9090 against [3H]iloprost (for IP receptors), [3H]PGE2 (for EP receptors) and [3H]SQ29,548 (for TP receptors) binding were 2803 +/- 327 nmol/l, 2509 +/- 1317 nmol/l and > 10000 nmol/l (n = 3), respectively. In contrast, TEI-7165 had high affinity for IP receptors (IC50 = 65.4 +/- 28.5 nmol/l, n = 3) but had moderate to low affinity for EP and TP receptors. The affinity of TEI-9090 for IP receptors was remarkably enhanced by pretreatment with rat serum as an esterase source. These findings suggest that TEI-9090 is converted to TEI-7165 by esterase, and that TEI-7165 exerts pharmacological effects through binding to IP receptors.
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002462:Cell Membrane / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D005343:Fibrinolytic Agents / Q000378:metabolism*; D006168:Guinea Pigs; D006834:Hydrazines / Q000378:metabolism; D016285:Iloprost / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism*; D051381:Rats; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D005343:Fibrinolytic Agents; D006834:Hydrazines; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; C052840:TEI 9090; C045749:SQ 29548; C041946:9-O-methanoprostaglandin I; D011464:Epoprostenol; D016285:Iloprost; D015232:Dinoprostone