Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury
© 2024. The Author(s)..
Homoeostatic regulation of the acid-base balance is essential for cellular functional integrity. However, little is known about the molecular mechanism through which the acid-base balance regulates cellular responses. Here, we report that bicarbonate ions activate a G protein-coupled receptor (GPCR), i.e., GPR30, which leads to Gq-coupled calcium responses. Gpr30-Venus knock-in mice reveal predominant expression of GPR30 in brain mural cells. Primary culture and fresh isolation of brain mural cells demonstrate bicarbonate-induced, GPR30-dependent calcium responses. GPR30-deficient male mice are protected against ischemia-reperfusion injury by a rapid blood flow recovery. Collectively, we identify a bicarbonate-sensing GPCR in brain mural cells that regulates blood flow and ischemia-reperfusion injury. Our results provide a perspective on the modulation of GPR30 signalling in the development of innovative therapies for ischaemic stroke. Moreover, our findings provide perspectives on acid/base sensing GPCRs, concomitantly modulating cellular responses depending on fluctuating ion concentrations under the acid-base homoeostasis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 27. Feb., Seite 1530 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jo-Watanabe, Airi [VerfasserIn] |
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| Links: |
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| Themen: |
Bicarbonates |
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| Anmerkungen: |
Date Completed 29.02.2024 Date Revised 01.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-45579-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Homoeostatic regulation of the acid-base balance is essential for cellular functional integrity. However, little is known about the molecular mechanism through which the acid-base balance regulates cellular responses. Here, we report that bicarbonate ions activate a G protein-coupled receptor (GPCR), i.e., GPR30, which leads to Gq-coupled calcium responses. Gpr30-Venus knock-in mice reveal predominant expression of GPR30 in brain mural cells. Primary culture and fresh isolation of brain mural cells demonstrate bicarbonate-induced, GPR30-dependent calcium responses. GPR30-deficient male mice are protected against ischemia-reperfusion injury by a rapid blood flow recovery. Collectively, we identify a bicarbonate-sensing GPCR in brain mural cells that regulates blood flow and ischemia-reperfusion injury. Our results provide a perspective on the modulation of GPR30 signalling in the development of innovative therapies for ischaemic stroke. Moreover, our findings provide perspectives on acid/base sensing GPCRs, concomitantly modulating cellular responses depending on fluctuating ion concentrations under the acid-base homoeostasis | ||
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| 650 | 7 | |a Calcium |2 NLM | |
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| 700 | 1 | |a Osada, Takahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Hashimoto, Ryota |e verfasserin |4 aut | |
| 700 | 1 | |a Nishizawa, Tomohiro |e verfasserin |4 aut | |
| 700 | 1 | |a Okuno, Toshiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Ihara, Sayoko |e verfasserin |4 aut | |
| 700 | 1 | |a Touhara, Kazushige |e verfasserin |4 aut | |
| 700 | 1 | |a Hattori, Nobutaka |e verfasserin |4 aut | |
| 700 | 1 | |a Oh-Hora, Masatsugu |e verfasserin |4 aut | |
| 700 | 1 | |a Nureki, Osamu |e verfasserin |4 aut | |
| 700 | 1 | |a Yokomizo, Takehiko |e verfasserin |4 aut | |
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