ROLE OF THE PURINERGIC P2Z RECEPTOR IN SPONTANEOUS CELL-DEATH IN J774MACROPHAGE CULTURES

J774 mouse macrophages express an ionotropic receptor gated by extrace llular ATP. Activation of this receptor, currently named purinergic P2 Z, causes transmembrane ion fluxes, plasma membrane depolarization, ce ll swelling and eventual cell death. The physiological role of this re ceptor is as yet unknown. In the present report we show that macrophag e cell clones that hypo-express the P2Z receptor showed a very low deg ree of spontaneous cell death in culture, while hyper-expressing clone s were exceedingly susceptible to cell death. To further support a rol e for ATP receptors in spontaneous cell death addition to the macropha ge cell cultures of oxidized ATP, a selective inhibitor of ionotropic purinergic receptors, or the ATP-hydrolysing enzyme apyrase, also redu ced spontaneous death. (C) 1996 Academic Press, Inc.