Genetic and pharmacological analysis of prostanoid receptor function

The availability of receptor knockouts and the use of expressed receptors to aid in the development of specific agonists and antagonists provide powerful tools for studying the biological importance of this group of bioactive lipids. This approach will be refined as tissue-specific inducible knockouts become available, and as mice carrying targeted mutations on a pure genetic background become more widely used. The combination of genetic approaches with the use of defined, specific pharmacological probes is likely to be extremely powerful. Examples of polymorphic variation in some prostanoid receptors have already been reported (39), and the relevance of these observations to disease susceptibility and interindividual variations in drug response is likely to become increasingly clear. While the role of prostanoids and associated compounds as nuclear receptor ligands is a seductive possibility, conclusive evidence that such events actually occur at concentrations of the endogenous compounds attained in vivo remains to be established.