Leukotriene B4 type 1 receptor (Leukotriene_B4_typ-1_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid metabolism. They can be divided into two classes, based on the presence or absence of a cysteinyl group. Leukotriene B4 (LTB4) does not contain such a group, whereas LTC4, LTD4, LTE4 and LTF4 are cysteinyl leukotrienes.

LTB4 is one of the most effective chemoattractant mediators known, and is produced predominantly by neutrophils and macrophages. It is involved in a number of events, including: stimulation of leukocyte migration from the bloodstream; activation of neutrophils; inflammatory pain; host defence against infection; increased interleukin production and transcription . It is found in elevated concentrations in a number of inflammatory and allergic conditions, such as asthma, psoriasis, rheumatoid arthritis and inflammatory bowel disease, and has been implicated in the pathogenesis of these diseases .

Binding sites for LTB4 have been observed in membrane preparations from leukocytes, macrophages and spleen. Two receptors for LTB4 have since been cloned (BLT1 and BLT2); both are members of the rhodopsin-like G-protein-coupled receptor superfamily .

The leukotriene B4 type 1 receptor (BLT1) has been cloned from Homo sapiens (Human), Mus musculus (Mouse) and Rattus norvegicus (Rat), and was found to be identical to a previously cloned receptor, P2Y7 . This receptor was originally thought to be a purinoceptor but is now widely accepted to bind LTB4. BLT1 has also been reported to act as a coreceptor for macrophage-tropic Human immunodeficiency virus 1 (HIV-1) strains . BLT1 is expressed primarily in peripheral leukocytes and peritoneal macrophages, with lower levels of expression detected in the spleen and thymus of humans . Activation of the receptor by LTB4 leads to the production of inositol trisphosphate and an increase in intracellular calcium levels. This response is sensitive to pertussis toxin in some cell types. The receptor also causes chemotaxis and inhibition of forskolin-stimulated adenylyl cyclase activity in a pertussis toxin sensitive manner. It has been demonstrated that BLT1 can couple to Gi2 and G16 G-proteins, depending on the cell type in which it is expressed .