Maintaining the proper acid-base balance is crucial for cellular function, and disruptions in this equilibrium can lead to various health issues. Membrane receptors, particularly G protein-coupled receptors (GPCRs), play a key role in monitoring changes in the extracellular environment. However, the significance of GPR30, also known as G protein-coupled estrogen receptor or membrane estrogen receptor, in cellular responses to acid-base disturbances has been unclear.
A recent study conducted by researchers at Juntendo University in Japan, led by Specially Appointed Associate Professor Airi Jo-Watanabe, sheds light on the role of GPR30 in cellular responses to pH variations. Published in Nature Communications, the research team, which includes co-authors Dr. Takehiko Yokomizo, Dr. Nobutaka Hattori, and Dr. Takahiro Osada, explored GPR30’s involvement in regulating cellular behavior in response to changes in bicarbonate concentrations.
The study aimed to identify a GPCR associated with the acid-base balance, leading researchers to focus on GPR30. Through their investigation, they discovered that GPR30 functions as a bicarbonate-sensing GPCR and plays a role in the pathophysiology of ischemic stroke.
The researchers identified GPR30 as a potential target for their study based on its high expression in brain microvasculature, where disruptions in the acid-base balance can occur due to pathological conditions like ischemia and reperfusion. By depleting bicarbonate from the culture medium, the team observed reduced GPR30 activation in vitro, indicating that bicarbonate activates GPR30.
Further experiments using mouse cell lines and GPR30 knock-in mice confirmed that GPR30 is activated by bicarbonate ions, particularly in brain microvasculature and pericytes. This activation hints at a potential mechanism for GPR30’s role in cerebrovascular regulation.
The researchers then investigated the role of GPR30 in cerebral ischemia-reperfusion injury, a critical aspect of ischemic stroke pathophysiology. They found that GPR30 deficiency in mice resulted in significant protection against injury, including reduced neurological deficits, blood-brain barrier disruption, and apoptotic cell death. Additionally, GPR30 deficiency improved blood flow recovery after ischemia-reperfusion injury, emphasizing its role in controlling blood flow in both large vessels and capillaries.
The study suggests that the bicarbonate buffer system modulates signal transduction in response to the extracellular environment, highlighting the connection between GPR30 and bicarbonate sensing in cerebrovascular health. These findings open up new possibilities for targeted strategies to mitigate the impact of ischemic stroke reperfusion injury and enhance vascular reactivity.
Dr. Jo-Watanabe believes that their research offers a novel approach to adjusting vascular reactivity through the bicarbonate receptor, potentially revolutionizing treatment strategies for cerebrovascular health.
In conclusion, this study represents a significant advancement in understanding the role of GPR30 in cerebrovascular regulation and offers promising prospects for developing innovative therapies for ischemic stroke treatment.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
