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 alpha beta methyleneATP, 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 alpha beta methyleneATP 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.