Structures and functions of the Prostanoid Receptors

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1.cDMAs for six types and subtypes of the prostanoid receptors of various species were cloned by the use of the cDNAs and nucleotide sequences of the thromboxane (TX) receptor (TP) and the prostaglandin (PG) E receptor EP3 subtype (EP3) we previously cloned. They include PGD receptor (DP) , PGE receptor EP1, EP2 and EP4 subtypes, PGF receptor (FP) and PGI receptor (IP) . Their structures, ligand binding specificities and signal transduction pathways were characterized.2.Genetic loci of these receptor genes on mouse chromosomes were determined, and gene structures of the human TP and IP were elucidated.3.The receptor isoforms of EP3 and TP created by altemative splicing were found. They were different only in the C-terminal tail but different in the signal transduction pathways.4.Distribution of these receptors in the body was revealed by northem blot analysis, and the detailed analysis by in situ hybridization were carried out for IP in mouse, for EP3 in mouse brain and for PGE receptor subtypes in mouse kidney. Specific functions were examined for TP in mouse thymus and in liver, and EP2 and EP3 in mouse brain.5.A point mutation was found in TP in patients with inherited bleeding disorder and identified as a cause of this disease.This work has thus clucidated molecular structures of all of the eight prostanoid receptors and provided the molecular basis for diverse physiological actions of the prostanoid molecules.