PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Activation of G Protein Coupled Estrogen Receptors (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway
Version 1
: Received: 17 May 2024 / Approved: 18 May 2024 / Online: 20 May 2024 (15:52:38 CEST)
How to cite:
Diaz-Zegarra, L. A.; Espejo, M. S.; Ibañez, A. M.; Rando, M. E.; Pagola, L. E.; De Giusti, V. C.; Aiello, E. A. Activation of G Protein Coupled Estrogen Receptors (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway. Preprints2024, 2024051213. https://doi.org/10.20944/preprints202405.1213.v1
Diaz-Zegarra, L. A.; Espejo, M. S.; Ibañez, A. M.; Rando, M. E.; Pagola, L. E.; De Giusti, V. C.; Aiello, E. A. Activation of G Protein Coupled Estrogen Receptors (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway. Preprints 2024, 2024051213. https://doi.org/10.20944/preprints202405.1213.v1
Diaz-Zegarra, L. A.; Espejo, M. S.; Ibañez, A. M.; Rando, M. E.; Pagola, L. E.; De Giusti, V. C.; Aiello, E. A. Activation of G Protein Coupled Estrogen Receptors (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway. Preprints2024, 2024051213. https://doi.org/10.20944/preprints202405.1213.v1
APA Style
Diaz-Zegarra, L. A., Espejo, M. S., Ibañez, A. M., Rando, M. E., Pagola, L. E., De Giusti, V. C., & Aiello, E. A. (2024). Activation of G Protein Coupled Estrogen Receptors (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway. Preprints. https://doi.org/10.20944/preprints202405.1213.v1
Chicago/Turabian Style
Diaz-Zegarra, L. A., Verónica Celeste De Giusti and Ernesto Alejandro Aiello. 2024 "Activation of G Protein Coupled Estrogen Receptors (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway" Preprints. https://doi.org/10.20944/preprints202405.1213.v1
Abstract
G-protein coupled estrogen receptor (GPER) was described to exerts several cardioprotective effects. However, the exact mechanism involved in cardiac protection remains unclear. The aim of this study is to investigate the role of GPER activation on excitation-contraction coupling (ECC), and the possibility that such effect participates in cardioprotection. Cardiac myocytes of male Wistar rats were isolated with digestive buffer and loaded with Fura-2-AM for measurement of intracellular calcium transients (CaT). Sarcomere shortening (SS) and L-type calcium current (ICaL) were also registered. Confocal technique was used to measure nitric oxide (NO) production in cells loaded with DAF-FM-diacetate. Cardiac myocytes exposed to E2 (10 nM), or G-1 (1 µM) for fifteen minutes decreased CaT, SS and ICaL. These effects were prevented using G-36 (antagonist of GPER, 1 µM), L-Name (NO synthase inhibitor, 100 nM), or wortmannin (phosphoinositide-3-kinase inhibitor, 100 nM). Moreover, G1 increased NO production, and this effect was abolished in the presence of wortmannin. We concluded that the selective activation of GPER with E2 or G1 in isolated cardiac myocytes of male rats induced a negative inotropic effect due to the reduction of ICaL and the decrease in CaT. Finally, the pathway that we proposed to be implicated in these effects is PI3K-NOS-NO.
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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