Background of Relaxin Receptors
The relaxin family peptide (RXFP) receptors are a family of G protein-coupled receptors, that mediate the hormonal and neuropeptide actions on their endogenous ligands relaxin family peptides and insulin-like peptides (INSL). Relaxin is characterized by vasodilatory, anti-fibrotic, angiogenic, anti-apoptotic, and anti-inflammatory properties, which has therapeutic effects on organ damage prevention, cardiovascular diseases, renal disease, and asthma. Chronic RXFP1 targeting therapies are under development.
Fig.1 Structural features of the relaxin family peptide receptor RXFP1. (Bathgate, 2013)
Distributions and Functions of Relaxin Receptors
The RXFP receptors are involved in the regulation of the cardiovascular system, formation of connective tissue and bone, reproduction, stress responses, anxiety and mood, arousal, spatial and social memory, and motivation. They are broadly distributed in the brain, reproductive tissues in both males and females, including semen, testis, ovary, pubic symphysis, cervix, uterus, and mammary glands, as well as in the heart, kidney, lung, thyroid, and colon.
Subtypes and Mechanisms of Relaxin Receptors
The family of RXFP receptors has 4 subtypes of G protein-coupled receptors, including RXFP1, RXFP2, RXFP3, and RXFP4 receptors. They promote signal transduction through Gs and Gi/Go proteins.
Receptor
|
Gene
|
Mechanism
|
Agonists
|
Antagonists
|
RXFP1 receptor
|
RXFP1
|
-
RXFP1 receptor couples with Gs protein to stimulate adenylyl cyclase
-
RXFP1 receptor couples with Gi/Go protein to inhibit adenylyl cyclase
-
RXFP1 receptor couples to Gi3, activating AC5 through Gβγ-PI3K-PKCζ pathway
|
-
[33P]relaxin
-
europium-labelled relaxin
-
INSL-3
-
TamRLX
-
coumpound54
|
|
RXFP2 receptor
|
RXFP2
|
-
RXFP2 receptor couples with Gs protein to stimulate adenylyl cyclase
-
RXFP2 receptor couples with Gi/Go protein to inhibit adenylyl cyclase
|
-
[33P]relaxin
-
[125I]INSL3
-
NanoLuc-INSL3
-
relaxin
-
relaxin-1
-
relaxin-3
-
TamRLX
|
-
A(9-26)INSL3
-
A(10-24)INSL3
-
A(C10/15S)INSL3
-
INSL3 B chain dimer analogue 8
-
A(Δ10/15C)INSL3
-
cyclic INSL3 B-chain analogue 6
|
RXFP3 receptor
|
RXFP3
|
-
RXFP3 receptor couples with Gi/Go protein to inhibit adenylyl cyclase
-
RXFP3 receptor activation leads to GTPγS binding as well as ERK1/2 and p38MAP kinase phosphorylation
-
RXFP3 receptor couples to Gi2 in CHO cells, while in HEK293 cells couples to Gi3, GOB, or GOA proteins
|
-
[125I]relaxin-3
-
[125I]relaxin-3-B/INSL5 A chimera
-
R3/I5- SmBiT
-
DOTA/Eu relaxin-3
-
B1-27
-
H3 14s18 stapled B-chain
|
-
europium-labelled R3(B1-22R)
-
minimised relaxin-3 analogue 3
-
R3 B1-22R
-
R3(BΔ23-27)R/I5 chimeric peptide
|
RXFP4 receptor
|
RXFP4
|
-
RXFP4 receptor couples with Gi/Go protein to inhibit adenylyl cyclase
-
RXFP4 receptor activation leads to ERK1/2, p38MAPK, Akt Ser473 and Thr308, and S6RP phosphorylation
|
-
[125I]relaxin-3
-
[125I]relaxin-3-B/INSL5 A chimera
-
R3/15
-
ΔR3/I5
-
compound 7a
|
-
R3(BΔ23-27)R/I5 chimeric peptide
-
INSL5-A13NR
-
minimised relaxin-3 analogue 3
|
RXFP1 RXFP3 RXFP4
Assay No.
|
Assay Name
|
Host Cell
|
Assay Type
|
Datasheet
|
cAMP Assay
|
S01YF-1122-KX856
|
Magic™ Rabbit RXFP1 In Vitro cAMP Assay
|
CHO-K1
|
cAMP Assay
|
|
S01YF-1122-KX857
|
Magic™ Rat RXFP1 In Vitro cAMP Assay
|
CHO-K1
|
cAMP Assay
|
|
S01YF-1122-KX853
|
Magic™ Dog RXFP1 In Vitro cAMP Assay
|
CHO-K1
|
cAMP Assay
|
|
Assay No.
|
Assay Name
|
Host Cell
|
Assay Type
|
Datasheet
|
Calcium Flux Assay
|
S01YF-1122-KX858
|
Magic™ Human RXFP3 In Vitro Calcium Flux Assay
|
CHO-K1
|
Calcium Flux Assay
|
|
[35S]GTPγS Binding Assay
|
S01YF-1122-KX860
|
Magic™ Human RXFP3 In Vitro [35S]GTPγS binding Assay
|
CHO-K1
|
[35S]GTPγS binding Assay
|
|
Assay No.
|
Assay Name
|
Host Cell
|
Assay Type
|
Datasheet
|
Calcium Flux Assay
|
S01YF-1122-KX861
|
Magic™ Human RXFP4 In Vitro Calcium Flux Assay
|
CHO-K1
|
Calcium Flux Assay
|
|
[35S]GTPγS Binding Assay
|
S01YF-1122-KX863
|
Magic™ Human RXFP4 In Vitro [35S]GTPγS binding Assay
|
CHO-K1
|
[35S]GTPγS binding Assay
|
|
S01YF-1122-KX864
|
Magic™ Mouse RXFP4 In Vitro [35S]GTPγS binding Assay
|
CHO-K1
|
[35S]GTPγS binding Assay
|
|
Reference
-
Bathgate, R. A. D.; et al. Relaxin family peptides and their receptors. Physiological reviews. 2013, 93(1): 405-480.
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