RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2 -Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway

Frontiers in Physiology
Xiaoming LianM Gollasch

Abstract

Background: Relaxins are small peptide hormones, which are novel candidate molecules that play important roles in cardiometablic syndrome. Relaxins are structurally related to the insulin hormone superfamily, which provide vasodilatory effects by activation of G-protein-coupled relaxin receptors (RXFPs) and stimulation of endogenous nitric oxide (NO) generation. Recently, relaxin could be demonstrated to activate Gi proteins and phosphoinositide 3-kinase (PI3K) pathways in cultured endothelial cells in vitro. However, the contribution of the Gi-PI3K pathway and their individual components in relaxin-dependent relaxation of intact arteries remains elusive. Methods: We used Gαi2- (Gnai2-/-) and Gαi3-deficient (Gnai3-/-) mice, pharmacological tools and wire myography to study G-protein-coupled signaling pathways involved in relaxation of mouse isolated mesenteric arteries by relaxins. Human relaxin-1, relaxin-2, and relaxin-3 were tested. Results: Relaxin-2 (∼50% relaxation at 10-11 M) was the most potent vasodilatory relaxin in mouse mesenteric arteries, compared to relaxin-1 and relaxin-3. The vasodilatory effects of relaxin-2 were inhibited by removal of the endothelium or treatment of the vessels with N (G)-nitro-L-arginine me...Continue Reading

References

May 2, 1992·Lancet·H KakourisR J Summers
May 10, 1991·Science·M I SimonN Gautam
Apr 1, 1991·The Journal of Clinical Endocrinology and Metabolism·D J HansellF C Greenwood
Jan 1, 1988·Cold Spring Harbor Symposia on Quantitative Biology·Y KaziroR Hernandez
Sep 1, 1995·British Journal of Pharmacology·T Bani-SacchiE Masini
Aug 15, 2001·The Journal of Comparative Neurology·M GotoN S Canteras
Jan 26, 2002·Science·Sheau Yu HsuAaron J W Hsueh
Feb 28, 2002·Cardiovascular Research·Mark A Sader, David S Celermajer
Jun 28, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Matthias LöhnArya M Sharma
Jul 18, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jacqueline NovakKirk P Conrad
Mar 21, 2003·Reproductive Biology and Endocrinology : RB&E·Silvia Nistri, Daniele Bani
Dec 3, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Galyna DubrovskaMaik Gollasch
Apr 15, 2004·Endocrine Reviews·O David Sherwood
Jun 16, 2005·Annals of the New York Academy of Sciences·Carmen W Dessauer, Bao T Nguyen
Sep 27, 2005·Physiological Reviews·Nina Wettschureck, Stefan Offermanns
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Mar 30, 2006·Molecular Pharmacology·Michelle L HallsRoger J Summers
Nov 2, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jacqueline NovakKirk P Conrad
Feb 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Antje GohlaBernd Nürnberg
Apr 14, 2007·Cardiovascular & Hematological Agents in Medicinal Chemistry·Silvia NistriDaniele Bani
Jul 10, 2007·Cardiovascular Research·Gábor FésüsMaik Gollasch
Jul 17, 2007·Cellular Signalling·Michele CiccarelliGuido Iaccarino
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Khaled AliBart Vanhaesebroeck
Mar 19, 2008·Hypertension·Gergö A MolnarAnette Fiebeler
Aug 5, 2008·Drug Discovery Today·Emma T van der WesthuizenRoger J Summers
May 7, 2009·Annals of the New York Academy of Sciences·Brigham J HartleyRoss A D Bathgate
Nov 26, 2009·Nature Reviews. Cardiology·Xiao-Jun DuRoger J Summers
Feb 9, 2010·Molecular and Cellular Endocrinology·Roy C K KongRoss A D Bathgate
May 26, 2010·Hypertension·Kirk P Conrad
Oct 12, 2010·Cardiology in Review·Jason Grossman, William H Frishman
Oct 28, 2010·Diabetes, Obesity & Metabolism·B M C McGowanS R Bloom
Feb 24, 2012·Nature·Andrew C KruseBrian K Kobilka
Nov 13, 2012·Lancet·John R TeerlinkUNKNOWN RELAXin in Acute Heart Failure (RELAX-AHF) Investigators
Dec 12, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristina WiegeJ Engelbert Gessner
Jan 11, 2013·Physiological Reviews·R A D BathgateR J Summers

❮ Previous
Next ❯

Citations

May 28, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Victoria L WolfMichael J Ryan
Sep 5, 2019·Biomolecules·Bernd Nürnberg, Sandra Beer-Hammer
Mar 4, 2020·The Journal of Biological Chemistry·Evi KostenisSuvi Annala
Jun 25, 2019·Frontiers in Physiology·Judit SimonEdit Gara
Jan 30, 2021·The Journal of Biological Chemistry·Evi KostenisSuvi Annala
Feb 28, 2021·The Journal of Biological Chemistry·Julian PattEvi Kostenis
Nov 14, 2020·Science·Junyue CaoJay Shendure

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic

Software Mentioned

GraphPad
Chart5
GraphPad Prism

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.