Molecular pathways of oestrogen receptors and -adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value
Author(s)
Machuki, JO
Zhang, HY
Harding, SE
Sun, H
Type
Journal Article
Abstract
Oestrogen receptors (ERs) and β‐adrenergic receptors (βARs) play important roles in the cardiovascular system. Moreover, these receptors are expressed in cardiac myocytes and vascular tissues. Numerous experimental observations support the hypothesis that similarities and interactions exist between the signalling pathways of ERs (ERα, ERβ and GPR30) and βARs (β1AR, β2AR and β3AR). The recently discovered oestrogen receptor GPR30 shares structural features with the βARs, and this forms the basis for the interactions and functional overlap. GPR30 possesses protein kinase A (PKA) phosphorylation sites and PDZ binding motifs and interacts with A‐kinase anchoring protein 5 (AKAP5), all of which enable its interaction with the βAR pathways. The interactions between ERs and βARs occur downstream of the G‐protein‐coupled receptor, through the Gαs and Gαi proteins. This review presents an up‐to‐date description of ERs and βARs and demonstrates functional synergism and interactions among these receptors in cardiac cells. We explore their signalling cascades and the mechanisms that orchestrate their interactions and propose new perspectives on the signalling patterns for the GPR30 based on its structural resemblance to the βARs. In addition, we explore the relevance of these interactions to cell physiology, drugs (especially β‐blockers and calcium channel blockers) and cardioprotection. Furthermore, a receptor‐independent mechanism for oestrogen and its influence on the expression of βARs and calcium‐handling proteins are discussed. Finally, we highlight promising therapeutic avenues that can be derived from the shared pathways, especially the phosphatidylinositol‐3‐OH kinase (PI3K/Akt) pathway.
Date Issued
2018-02-01
Date Acceptance
2017-10-02
Citation
ACTA PHYSIOLOGICA, 2018, 222 (2)
ISSN
1748-1708
Publisher
WILEY
Journal / Book Title
ACTA PHYSIOLOGICA
Volume
222
Issue
2
Copyright Statement
© 2017 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Medical Research Council (MRC)
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000423367700021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/M010422/1
FS/16/52/32259
Subjects
Science & Technology
Life Sciences & Biomedicine
Physiology
beta-adrenergic receptors
cardioprotection
crosstalk
GPR30
intracellular signalling
oestrogen receptors
PROTEIN-COUPLED RECEPTOR
HUMAN ENDOTHELIAL-CELLS
CA2+ CHANNEL CA(V)1.2
SMOOTH-MUSCLE-CELLS
ALPHA ER-ALPHA
UP-REGULATION
NITRIC-OXIDE
SARCOPLASMIC-RETICULUM
HEART-FAILURE
FEMALE RATS
Publication Status
Published
Article Number
e12978
Date Publish Online
2017-10-30