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.

• Authors: M Tanaka, C Kojima, M Muramatsu, H Tanabe
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 45 Issue 9 Pg. 967-70 (Sep 1995) ISSN: 0004-4172 [Print] Germany
• PMID: 7488314 (Publication Type: Journal Article)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Fatty Acids, Unsaturated
• Fibrinolytic Agents
• Hydrazines
• Platelet Aggregation Inhibitors
• Receptors, Prostaglandin
• TEI 9090
• SQ 29548
• 9-O-methanoprostaglandin I
• Epoprostenol
• Iloprost
• Dinoprostone

Topics

• Animals
• Blood Platelets (metabolism)
• Bridged Bicyclo Compounds, Heterocyclic
• Cell Membrane (metabolism)
• Dinoprostone (metabolism)
• Epoprostenol (analogs & derivatives, metabolism)
• Fatty Acids, Unsaturated
• Fibrinolytic Agents (metabolism)
• Guinea Pigs
• Hydrazines (metabolism)
• Iloprost (metabolism)
• In Vitro Techniques
• Mice
• Platelet Aggregation Inhibitors (metabolism)
• Rats
• Receptors, Prostaglandin (metabolism)
• Tumor Cells, Cultured