A new neurogenic receptor activator of P2Y1——Up4A


Recently, researchers from Nevada School of Medicine found a novel factor, uridine adenosine tetraphosphate (Up4A), may contribute in mediating enteric inhibitory neurotransmission of the intestines, acts through P2Y1 receptors (P2Y1Rs) and apamin-sensitive small-conductance Ca2+ -activated K+ (SK) channels. The article was published on PNAS.


In functional gastrointestinal (GI) mobility disorders, muscular spasms can cause pain, or contractions changing the speed or direction of gut transit. Neural regulation of GI motility involved two key mediators, P2Y1Rs and SK channels. They regulate inhibitory neurons in the GI tract. Researchers found Up4A can activate P2Y1R and SK channels, leads to colonic muscles relaxation both in human and murine colons. Further examination showed Up4A binds to P2Y1R to activate SK chennels in PDGFRα+ cells. The electrophysiological responses to Up4A were investigated then, to determine the mechanism of contractile responses they observed. Up4A caused transient hyperpolarization responses in murine intact muscles and in PDGFRα+ cells. Also ,they found Up4A is released spontaneously and depend on nerve stimulation in human and murine colons.


The results revealed that Up4A, as a novel factor, may contribute to the regulation of enteric inhibitory neurotransmission that mediated by P2Y1R and SK channels.


Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15821-6

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