Diinosine pentaphosphate: an antagonist which discriminates between recombinant P2X 3 and P2X 2/3 receptors and between two P2X receptors in rat sensory neurones

We have compared the antagonist activity of trinitrophenyl‐ATP (TNP‐ATP) and diinosine pentaphosphate (Ip 5 I) on recombinant P2X receptors expressed in Xenopus oocytes with their actions at native P2X receptors in sensory neurones from dorsal root and nodose ganglia. Slowly‐desensitizing responses to α,β‐methylene ATP (α,β‐meATP) recorded from oocytes expressing P2X 2/3 receptors were inhibited by TNP‐ATP at sub‐micromolar concentrations. However, Ip 5 I at concentrations up to 30 μ M was without effect. Nodose ganglion neurones responded to α,β‐meATP with slowly‐desensitizing inward currents. These were inhibited by TNP‐ATP (IC 50 , 20 n M ), but not by Ip 5 I at concentrations up to 30 μ M . In DRG neurones that responded to ATP with a rapidly‐desensitizing inward current, the response was inhibited by TNP‐ATP with an IC 50 of 0.8 n M . These responses were also inhibited by Ip 5 I with an IC 50 of 0.1 μ M . Both antagonists are known to inhibit homomeric P2X 3 receptors. Some DRG neurones responded to α,β‐meATP with a biphasic inward current, consisting of transient and sustained components. While the transient current was abolished by 1 μ M Ip 5 I, the sustained component remained unaffected. In conclusion, Ip 5 I is a potent antagonist at homomeric P2X 3 receptors but not at heteromeric P2X 2/3 receptors, and therefore should be a useful tool for elucidating the subunit composition of native P2X receptors.British Journal of Pharmacology (2000) 130 , 1378–1384; doi: 10.1038/sj.bjp.0703404