The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca Handling.
Holm, Anders LU ; Hellstrand, Per LU ; Olde, Björn LU ; Svensson, Daniel LU ; Leeb-Lundberg, Fredrik LU and Nilsson, Bengt-Olof LU
(2013)
In Journal of Vascular Research
50(5).
p.421-429
- Abstract
- The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity but had no effect on the U46619-induced increase in the basal level of Ca(2+). The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced Ca(2+) spike activity similar to G-1.... (More)
- The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity but had no effect on the U46619-induced increase in the basal level of Ca(2+). The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced Ca(2+) spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca(2+) spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca(2+) spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca(2+) concentration, suggesting that G-1 blocks inflow of Ca(2+) via voltage-sensitive Ca(2+) channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca(2+) handling by lowering Ca(2+) spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure. © 2013 S. Karger AG, Basel. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4143815
- author
- Holm, Anders
LU
; Hellstrand, Per
LU
; Olde, Björn
LU
; Svensson, Daniel
LU
; Leeb-Lundberg, Fredrik
LU
and Nilsson, Bengt-Olof
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Vascular Research
- volume
- 50
- issue
- 5
- pages
- 421 - 429
- publisher
- Karger
- external identifiers
-
- wos:000326362700006
- pmid:24080531
- scopus:84886790262
- pmid:24080531
- ISSN
- 1423-0135
- DOI
- 10.1159/000354252
- language
- English
- LU publication?
- yes
- id
- c2b93364-bb9e-4153-a3f3-714c9c00d910 (old id 4143815)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24080531?dopt=Abstract
- date added to LUP
- 2016-04-01 09:50:06
- date last changed
- 2022-03-27 01:19:37
@article{c2b93364-bb9e-4153-a3f3-714c9c00d910,
abstract = {{The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity but had no effect on the U46619-induced increase in the basal level of Ca(2+). The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced Ca(2+) spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca(2+) spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca(2+) spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca(2+) concentration, suggesting that G-1 blocks inflow of Ca(2+) via voltage-sensitive Ca(2+) channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca(2+) handling by lowering Ca(2+) spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure. © 2013 S. Karger AG, Basel.}},
author = {{Holm, Anders and Hellstrand, Per and Olde, Björn and Svensson, Daniel and Leeb-Lundberg, Fredrik and Nilsson, Bengt-Olof}},
issn = {{1423-0135}},
language = {{eng}},
number = {{5}},
pages = {{421--429}},
publisher = {{Karger}},
series = {{Journal of Vascular Research}},
title = {{The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca Handling.}},
url = {{https://lup.lub.lu.se/search/files/1301822/4255804.pdf}},
doi = {{10.1159/000354252}},
volume = {{50}},
year = {{2013}},
}