THE PERMEABILIZING ATP RECEPTOR, P2X(7) - CLONING AND EXPRESSION OF AHUMAN CDNA

A cDNA was isolated from a human monocyte library that encodes the P2X (7) receptor; the predicted protein is 80% identical to the rat recept or, Whole cell recordings were made from human embryonic kidney cells transfected with the human cDNA and from human macrophages, Brief appl ications (1-3 s) of ATP and 2',3'-(4-benzoyl)-benzoyl-ATP elicited cat ion-selective currents, When compared with the rat P2X(7) receptor, th ese effects required higher concentrations of agonists, were more pote ntiated by removal of extracellular magnesium ions, and reversed more rapidly on agonist removal. Longer applications of agonists permeabili zed the cells, as evidenced by uptake of the propidium dye YO-PRO1, bu t this was less marked than for cells expressing the rat P2X(7) recept or, Expression of chimeric molecules indicated that some of the differ ences between the rat and human receptor could be reversed by exchangi ng the intracellular C-terminal domain of the proteins.