Structure and function of prostanoid receptors.

Abstract

We have recently cloned cDNAs for the human and mouse TXA2/PGH2 receptors and a cDNA for the mouse PGE receptor. Sequencing, homology and hydrophobicity analyses revealed that they are proteins of 343, 341 and 365 amino acid residues, respectively, and all are rhodopsin-type receptors with putative seven transmembrane domains. Homology between the human and mouse TXA2 receptors is 76% in total and that between the human TXA2 and mouse PGE receptors is 38%. The homology increases in the putative transmembrane regions to 85 and 45%, respectively, and there observed several features common to the three receptors. These results indicate that the prostanoid receptors constitute a family of receptors of similar structure. The cloned PGE receptor showed binding activity specific to so-called EP3 agonists, which verified for the first time that pharmacologically defined PGE receptor subtypes consist of different molecules. This receptor also displayed different efficiency in signal transduction to an EP3 agonist, M & B-28767, and PGE2, providing an interesting model for the analysis of receptor-G protein coupling. In addition to the above biochemical results, these studies have revealed the characteristic tissue distribution of these receptors, which will open up a new biology of these prostanoids.