Molecular cloning and characterization of another leukotriene B-4 receptor

Leukotriene B-4 is a potent lipid mediator known to be implicated mainly in inflammatory actions. Previous pharmacological studies indicated the exist ence of only one class of G protein-coupled receptor for leukotriene B-4, f or which a candidate gene, namely BLT, had been identified. Here we report the isolation of another gene encoding a functional G protein-coupled recep tor for leukotriene B-4, named JULF2. JULF2 is a novel G protein-coupled re ceptor of 358 amino acids that shares 36.6% amino acid identity with human BLT, According to genomic information, the JULF2 gene is located on the chr omosome 14, about 4 kilobases upstream of the BLT gene. During screening of endogenous ligands for JULF2, we found that leukotriene B-4 induced inhibi tion of forskolin-stimulated cAMP accumulation in Chinese hamster ovary cel ls, stably expressing JULF2, Additionally, Chinese hamster ovary cells expr essing exogenous JULF2 showed chemotactic responses with leukotriene B-4 in a pertussis toxin-sensitive manner. A large amount of JULF2 mRNA was detec ted in the human spleen and the peripheral blood leukocytes. Furthermore, J ULF2 mRNA was expressed in mononuclear lymphocytes, in which BLT mRNA was b arely detected. The discovery of this second leukotriene B-4 receptor will eventually lead to a better understanding of the classification of leukotri ene B-4 receptors and reconsideration of the pathophysiological role of leu kotriene B-4.