| RRC ID |
78335
|
| Author |
Jo-Watanabe A, Inaba T, Osada T, Hashimoto R, Nishizawa T, Okuno T, Ihara S, Touhara K, Hattori N, Oh-Hora M, Nureki O, Yokomizo T.
|
| Title |
Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury.
|
| Journal |
Nat Commun
|
| Abstract |
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.
|
| Volume |
15(1)
|
| Pages |
1530
|
| Published |
2024-2-27
|
| DOI |
10.1038/s41467-024-45579-3
|
| PII |
10.1038/s41467-024-45579-3
|
| PMID |
38413581
|
| PMC |
PMC10899177
|
| MeSH |
Animals
Bicarbonates
Brain Ischemia*
Calcium / metabolism
Male
Mice
Receptors, Estrogen / metabolism
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism
Reperfusion Injury*
Stroke*
|
| Resource |
| Human and Animal Cells |
C2C12(RCB0987) |
