Disease relevance of RXFP4

• In contrast, RXFP3 and RXFP4 couple to Gi by a pertussis toxin-sensitive mechanism to cause inhibition of cAMP production [1].
• Full-length GPR100 was amplified from a cDNA library of the neuroendocrine cell line BON, which is derived from a human pancreas carcinoid [2].

High impact information on RXFP4

• In a saturation binding assay, (125)I-INSL5 binds GPCR142 with a K(d) value of 2.5 nM [3].
• Overall, INSL5 behaves as an agonist for GPCR142 similar to relaxin-3 [3].
• In functional guanosine (gamma-thio)-triphosphate binding and cAMP accumulation assays, INSL5 potently activates GPCR142 with EC(50) values of 1.3 and 1.2 nM, respectively [3].
• Analysis of possible receptors related to GPCR135 revealed a single orphan receptor, GPCR142 [4].
• We evaluated by reverse transcriptase-PCR the expression of GPCR142 mRNA in a variety of human tissues and found expression in brain, kidney, testis, thymus, placenta, prostate, salivary gland, thyroid, and colon [4].

Biological context of RXFP4

• The rat GPCR142 gene was found to be a pseudogene [5].
• The analysis of chromosomal localisation mapped the GPR100 gene to chromosome 1q21.2-q21 [2].
• Bradykinin B2 and GPR100 receptors: a paradigm for receptor signal transduction pharmacology [6].
• G-protein-coupled receptor 100 (GPR100) was discovered by searching the human genome database for novel G-protein-coupled peptide receptors [2].

Associations of RXFP4 with chemical compounds

• In addition, INSL5 stimulates Ca(2+) mobilization in HEK293 cells expressing GPCR142 and G alpha(16) [3].
• Boels and Schaller recently reported bradykinin as a ligand for GPCR142 (also known as GPR100) [5].
• The nonpeptide B(2) receptor agonist FR190997 (8-[2,6-dichloro-3-[N-methylcarbamoyl)cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline) did inhibit the forskolin-induced cAMP production (pEC(50) = 7.7) at the hB(2)R, whereas it was not able to exert any effect at the hGPR100 [6].
• FR190997 and relaxin 3 responses at the hB(2)R and hGPR100, respectively, were not inhibited by Icatibant (1 microM) [6].

Regulatory relationships of RXFP4

• Surprisingly, GPCR142 was activated by nanomolar concentrations of relaxin-3 but was completely unresponsive to all other known insulin-like peptides [4].

Other interactions of RXFP4

• In this report, we demonstrate that INSL5 is a specific agonist for GPCR142 [3].
• Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor [2].
• The aim of the present report was to investigate the ligand selectivity of the human orphan G-protein-coupled receptor GPR100 (hGPR100), recently identified as a novel bradykinin (BK) receptor, as compared with that of the human B(2) receptor (hB(2)R) stably transfected in Chinese hamster ovary cells [6].

Analytical, diagnostic and therapeutic context of RXFP4

• 3. The stable expression of GPR100 in Chinese hamster ovary cells together with aequorin as calcium sensor and the promiscuous G-protein subunit alpha16 as signal transducer revealed bradykinin and kallidin as effectors to elicit a calcium response [2].

References