BPTU is a P2Y1 allosteric antagonist as an antithrombotic agent, which binds receptor entirely outside of the helical bundle. BPTU dose-dependently inhibited purinergic inhibitory junction potentials and inhibition of spontaneous motility induced by electrical field stimulation in the colon of rats (EC50 = 0.3 μM) and mice (EC50 = 0.06 μM) [1].BPTU blocked colon nicotine induced relaxation in the rat colon[1]. In the rat colon, the P2Y agonist ADPβS at 10 μM significantly reduces spontaneous contractions, and this reduction is blocked by BPTU at a concentration of 3 μM[1]. Also, the selective P2Y1 agonist MRS2365, at a concentration of 5 μM significantly reduces spontaneous contractions in the murine colon, and this reduction is blocked by BPTU at a concentration of 3 μM[1].BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, located entirely outside of the helical bundle[2]. BPTU prefers partitioning into the interface of polar/lipophilic region of the lipid bilayer before associating with the receptor[3]. Then, it interacts with the second extracellular loop of the receptor and reaches the binding site through the lipid-receptor interface[3].
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