Pharmacology of Cloned P2X Receptors

There are seven P2X receptor cDNAs currently known. Six homomeric (P2X 1 , P2X 2 , P2X 3 , P2X 4 , P2X 5 , P2X 7 ) and three heteromeric (P2X 2 /P2X 3 , P2X 4 /P2X 6 , P2X 1 /P2X 5 ) P2X receptor channels have been characterized in heterologous expression systems. Homomeric P2X 1 and P2X 3 receptors are readily distinguishable by their rapid desensitization, the agonist action of αβmethyleneATP, and the block by 2′,3′-O-(2,4,6-trinitrophenyl)-ATP. P2X 2 receptors are unique among homomeric forms in their potentiation by low pH. Homomeric P2X 4 receptors are much less sensitive to antagonism by suramin and pyridoxal 5-phosphate-6-azo-2′,4′-disulfonic acid. Homomeric P2X 7 receptors are the only form in which 2′,3′-O-(4-benzoylbenzoyl)-ATP is more potent than ATP. The heteromeric P2X 2 /P2X 3 receptor resembles P2X 2 in slow desensitization kinetics and potentiation by low pH and is similar to P2X 3 with respect to agonism by αβmethyleneATP and block by 2′,3′-O-(2,4,6-trinitrophenyl)-ATP. Other agonists, antagonists, and ions that can be used to differentiate among the receptors are discussed.