Prostanoid receptors: Subtypes and signaling

Cyclooxygenases metabolize arachidonate to five primary prostanoids: PGE(2) , PGF(2 alpha), PGI(2), TxA(2), and PGD(2). These autacrine lipid mediators interact with specific members of a family of distinct G-protein-coupled p rostanoid receptors, designated EP, FP, IP, TP, and DP, respectively. Each of these receptors has been cloned, expressed, and characterized. This fami ly of eight prostanoid receptor complementary DNAs encodes seven transmembr ane proteins which are typical of G-protein-coupled receptors and these rec eptors are distinguished by their ligand-binding profiles and the signal tr ansduction pathways activated on ligand binding. Ligand-binding selectivity of these receptors is determined by both the transmembrane sequences and a mino acid residues in the putative extracellular-loop regions. The selectiv ity of interaction between the receptors and G proteins appears to be media ted at least in part by the C-terminal tail region. Each of the EP1, EP3, F P, and TP receptors has alternative splice variants described that alter th e coding sequence in the C-terminal intracellular tail region. The C-termin al variants modulate signal transduction, phosphorylation, and desensitizat ion of these receptors, as well as altering agonist-independent constitutiv e activity.