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Trimeric Scaffold Ligand-Gated Ion Channels
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Xiao-Na Yang, Si-Yu Wang, Jin Wang, Ye Yu
The P2X receptor is one of TS-LGICs that could be directly activated by extracellular ATP, and seven different P2X subtypes have been identified so far, named as P2X1, P2X2, P2X3, P2X4, P2X5, P2X6, and P2X7 receptors (8). Wide distribution of these various P2X subtypes allows them to participate in diverse physiological processes, for instance, neural signaling, learning and memory, pain sensation, and immunological, respiratory, cardiovascular, and genitourinary functions regulations (9–14). Disturbing channel functions mentioned above are considered to be relevant, also as important strategies in drug developments of many diseases like rheumatoid arthritis, mood disorder, stroke, neuropathic pain, and thrombogenesis (15–17). At present a series of P2X receptor-targeted small molecules have been in the main phase of clinical trials or pre-clinical stage aiming to treat rheumatoid arthritis, unexplained/refractory chronic cough, depression, and pain syndromes (18–21).
GDNF enhances human blood-nerve barrier function in vitro via MAPK signaling pathways
Published in Tissue Barriers, 2018
Chaoling Dong, Eroboghene E. Ubogu
Endothelial cells are serum-dependent for attachment, and serum withdrawal is associated with diffuse reduction in continuous intercellular membrane contacts in sub-confluent proliferating cells.46 However, serum withdrawal is also a well-established technique to suppress growth, induce contact-inhibition and promote intercellular junction formation by confluent epithelial and endothelial cells in vitro.50-52 The effect of GDNF, RET-tyrosine kinase and MAPK signaling in maintaining a high TEER following serum withdrawal was confirmed at the human BNB in vitro. Schwann cells are the primary source of GDNF in peripheral nerves in vivo.12,53,54 The current study suggests that purinergic receptor P2RX6 may be involved in the human BNB endothelial cell response to serum withdrawal due to its high transcript expression levels under basal conditions without exogenous GDNF. This hypothesis is supported by a recent publication that demonstrated activation of Schwann cell P2 type purinergic receptors following sciatic nerve injury that resulted in induced GDNF transcription in adult male Sprague-Dawley rats.54