Binding affinities of isocarbacyclin methyl ester and its free acid to prostanoid receptors
Tanaka, M.; Kojima, C.; Muramatsu, M.; Tanabe, H.
Arzneimittel-Forschung 45(9): 967-970
1995
ISSN/ISBN: 0004-4172 PMID: 7488314 Document Number: 442074
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) I-2 receptors (IP receptors), PGE-2 receptors (EP receptors) and thromboxane A-2 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 IC-50 values of TEI-9090 against (3H)iloprost (for IP receptors), (3H)PGE-2 (for EP receptors) and (3H)SQ29,548 (for TP receptors) binding were 2803 +- 327 nmol/l, 2509 +- 1317 nmol/l and gt 10000 nmol/l (n = 3), respectively. In contrast, TEI-7165 had high affinity for IP receptors (IC-50 = 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.