Studies on the characterisation of prostanoid receptors: a proposed classification

Abstract

Comparison of rank orders of agonist potency of the naturally occurring prostanoids, PGD2, PGE2, PGF2 alpha and PGI2 as well as the stable TxA2 mimetic, U-46619, on a range of smooth muscle preparations provides evidence for the existence of distinct receptors for PGE2, PGF2 alpha and TxA2. Since others have provided evidence for the existence of distinct receptors for PGD2 and PGI2, we suggest that receptors exist for each of these naturally occurring 2-series prostanoids. Results obtained with two specific prostanoid receptor blocking drugs, SC-19220 and AH 19437, support and extend these conclusions. SC-19220 selectively blocks some but not all PGE-sensitive receptors, while AH 19437 selectively blocks all U-46619/TxA2-sensitive receptors. A nomenclature for prostanoid receptors is proposed, in which each receptor is designated the letter P preceded by a letter signifying the most potent natural prostanoid agonist at that receptor, such that receptors sensitive to PGs D2, E2, F2 alpha, I2 and TxA2 become DP-, EP-, FP-, IP and TP- receptors respectively. Where some sub-division is required within a receptor group, e.g. EP-receptors (SC-19220-sensitive and SC-19220-insensitive), subscript numbers may be used such that these are EP1 and EP2 subtypes. The resulting scheme is a working hypothesis and its confirmation requires the development of potent selective prostanoid receptor blocking drugs for each postulated type.