Prostanoid Receptors

Abstract

Functional. The functional approach to receptor classification was pioneered by Ahlquist (1948), who demonstrated that adrenoceptors could be subclassified into α-and β-subtypes on the basis of the rank order of potency of a series of cathecholamines. Although the power of this approach was not immediately acknowledged, it gradually became accepted, and has now been utilised in the classification of most if not all known hormone receptors. It has been of crucial importance in the classification of prostanoid receptors, leading to the now generally accepted conclusion that there are receptors specific for each of the naturally occurring prostanoids, and that there are subtypes of at least one of these (Coleman et al., 1994b). The first tentitive steps towards the classification of prostanoid receptors were made by Pickles in 1967, who reported that a range of different prostanoid analogues exhibited different rank orders of agonist potency in a range of different tissues. This report was followed by those of Andersen and Ramwell (1974), Andersen et al. (1980) and Gardiner and Collier (1980), who provided further evidence for distinct rank orders of prostanoid agonist potency in different systems both in vitro and in vivo. However, it was the work of Kennedy et al. (1982) that provided the basis for the classification of prostanoid receptors that is now universally accepted (see Coleman et al., 1994b, Table 1). This classification states that there are five basic classes of receptor, DP, EP, FP, IP and TP, with subdivision of the EP class into four subtypes, EP₁, EP₂, EP₃ and EP₄. As yet, there is no conclusive evidence of subtypes of any of the other four classes, but it seems unlikely that such subdivision is restricted to EP-receptors, and it has been suggested that there are subtypes of both DP and TP-receptors. Further subdivision of EP-receptors is now apparent following the discovery that there are a number of isoforms of the EP₃-receptor class (Namba et al., 1993).