G protein-coupled adenosine receptor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals generated as a consequence of a receptor binding to extracellular adenosine and transmitting the signal to a heterotrimeric G-protein complex to initiate a change in cell activity. [GOC:dph]

The G protein-coupled adenosine receptor (GPCR) signaling pathway is a critical cellular communication system involved in a wide range of physiological processes. It is activated by adenosine, a ubiquitous nucleoside that plays a vital role in regulating various cellular functions. The pathway begins with the binding of adenosine to its cognate GPCRs, known as A1, A2A, A2B, and A3 receptors. These receptors are transmembrane proteins with seven transmembrane domains that span the cell membrane. Upon adenosine binding, the receptor undergoes a conformational change, triggering the activation of heterotrimeric G proteins. G proteins are composed of three subunits: alpha (α), beta (β), and gamma (γ). The α subunit is responsible for binding to GDP and GTP, while the βγ subunits act as a dimer. In the inactive state, the α subunit is bound to GDP and associated with the βγ subunits. Upon receptor activation, the α subunit exchanges GDP for GTP. This GTP-bound α subunit dissociates from the βγ dimer and interacts with downstream signaling molecules, initiating a cascade of intracellular events. The specific downstream signaling pathways activated by GPCRs depend on the specific receptor subtype and the associated G protein. For example, A1 receptors are typically coupled to Gi/o proteins, which inhibit adenylyl cyclase activity, leading to a decrease in cAMP levels. This reduction in cAMP can influence various cellular processes, such as reducing heart rate, promoting vasodilation, and inhibiting neurotransmitter release. Conversely, A2A and A2B receptors are typically coupled to Gs proteins, which activate adenylyl cyclase, leading to an increase in cAMP levels. Increased cAMP can lead to various cellular responses, such as increasing heart rate, promoting bronchodilation, and stimulating insulin secretion. A3 receptors are typically coupled to Gi/o proteins, which can also activate phospholipase C (PLC), leading to the production of inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 triggers the release of calcium from intracellular stores, while DAG activates protein kinase C (PKC). These signaling events can modulate a variety of cellular functions, including cell proliferation, apoptosis, and inflammation. In addition to activating downstream signaling pathways, GPCRs can also interact with other cellular components, such as scaffolding proteins and adaptor molecules. These interactions can further modulate the signaling cascade, fine-tuning the cellular response to adenosine. Overall, the GPCR signaling pathway is a complex and highly regulated system that plays a critical role in maintaining cellular homeostasis and mediating a wide range of physiological functions. It is essential for regulating heart rate, blood pressure, neurotransmission, inflammation, and many other critical processes. Dysregulation of the GPCR signaling pathway has been implicated in various diseases, including cardiovascular disease, neurological disorders, and cancer.'
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Proteins (10)

Compounds (474)