Disease relevance of RXFP3

• In contrast, RXFP3 and RXFP4 couple to Gi by a pertussis toxin-sensitive mechanism to cause inhibition of cAMP production [1].

High impact information on RXFP3

• INSL5 inhibits (125)I-relaxin-3 binding to GPCR135 with a low potency (K(i) = 500 nM) [2].
• GPCR135 is expressed abundantly in the hypothalamus with discrete expression in the paraventricular nucleus of the hypothalamus and supraoptic nucleus, as well as in the cortex, septal nucleus, and preoptical area [3].
• GPCR135, publicly known as somatostatin- and angiotensin-like peptide receptor, is expressed in the central nervous system and its cognate ligand(s) has not been identified [3].
• The identification of relaxin-3 as the ligand for GPCR135 provides the framework for the discovery of a new brainstem/hypothalamus circuitry [3].
• We have found that both rat and porcine brain extracts stimulated 35S-labeled guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) incorporation in cells over-expressing GPCR135 [3].

Biological context of RXFP3

• The GPCR135 mRNA distribution generally overlaps the pattern of GPCR135 binding sites shown by autoradiography using [(125)I]R3/I5 [4].
• Chromosomal mapping by radiation hybrid analysis localized the human SALPR gene to the chromosome 5p15.1-5p14 [5].
• The functional response to H3 relaxin and other relaxin/insulin peptides of GPCR135 expressed in CHO-K1 cells was measured in the cytosensor microphysiometer and analyzed using inhibitors of signal transduction proteins [6].

Anatomical context of RXFP3

• Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the SALPR mRNA is predominantly expressed in human brain regions, particularly the substantia nigra and pituitary, although the mRNA can also be detected in the peripheral tissues, albeit at low levels [5].
• Transient expression of SALPR in COS-1 cells did not produce any binding sites for somatostatin or angiotensin II, indicating the necessity for further study to discover its ligand and physiological significance [5].
• The mouse orthologue of somatostatin and angiotensin-like peptide receptor (SALPR) was amplified from cDNA of the hippocampal cell line HT22 [7].
• A distinct pattern of expression in brain, spinal cord, and dorsal root ganglia during development and in the mature brain hint at important functions of SALPR for differentiation and maintenance of the nervous system [7].

Other interactions of RXFP3

• A functional assay shows that INSL5 (1 microm) is a weak antagonist for GPCR135 [2].
• In the accompanying article (Liu, C., Eriste, E., Sutton, S., Chen, J., Roland, B., Kuei, C., Farmer, N., Jörnvall, H., Sillard, R., and Lovenberg, T. W. (2003) J. Biol. Chem. 278, 50754-50764), we present the case that relaxin-3, which has previously been shown to bind to the relaxin receptor LGR7, is most likely the endogenous ligand for GPCR135 [8].
• The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors [5].
• G-protein-coupled receptor gene [somatostatin and angiotensin-like peptide receptor (SALPR)] is one of the candidate genes within the critical interval [9].

References