New research conducted at The University of Texas Medical Branch has shed light on the connection between Pannexin-1 channels, extracellular adenosine triphosphate (ATP), and purinergic receptors in the development of infectious diseases such as HIV and SARS-CoV-2. The study has uncovered potential therapeutic applications that could help mitigate the devastating effects of these viral threats.
Purinergic signaling, which involves the activation of purinergic receptors by purine nucleotides and nucleosides, plays a crucial role in viral infections. During an infection, inflammation is triggered, leading to the activation of Panx1 and the release of ATP and K+ ions, as well as the influx of Ca++. ATP is released from the cell through the Panx1 channel and binds to P2Y and P2X receptors, while AMP is converted to adenosine. These interactions further stimulate the adenosine receptor, which suppresses inflammatory responses.
While researchers have extensively studied the role of purinergic signaling in various diseases, its significance in emerging diseases has only recently been recognized. Under normal conditions, the immune system regulates the response to ATP through the rapid degradation of purine nucleotides. However, during infections, an increase in ATP levels disrupts this regulation, leading to chronic inflammatory states.
ATP also plays a crucial role in immune activation by enhancing T cell activation and antigen presentation. It enhances the immune response of various immune cells and contributes to cellular migration and lymphocyte activation. However, high ATP levels can inhibit lymphocyte activation and migration, impairing immune surveillance and antigen presentation.
Macrophages and microglia, two types of immune cells, are also affected by ATP signaling. In response to ATP, M1 macrophages, which have proinflammatory properties, produce proinflammatory cytokines. ATP also activates P2Y receptors, contributing to the differentiation and activation of monocytes, macrophages, and microglia.
Pannexin-1 channels, which open in response to specific stimuli, play a crucial role in the release of ATP during inflammatory conditions. This release of ATP can activate signaling pathways that promote oxidative stress, tissue injury, and inflammation. In the context of COVID-19, the dysregulation of the renin-angiotensin signaling pathway leads to the activation of PANX1 channels and the release of ATP, contributing to COVID-19 complications.
Understanding the intricate interplay between Pannexin-1 channels, extracellular ATP, and purinergic receptors presents exciting possibilities in the field of infectious disease research. By unraveling these molecular mechanisms, researchers may be able to develop innovative therapeutic interventions to combat infectious diseases and safeguard human health. Targeting PANX1 and purinergic signaling pathways with repurposed FDA-approved drugs or developing new drugs that directly target PANX1 channels or purinergic receptors could offer potential treatment options for COVID-19 and other infectious diseases.