NON-GENOMIC INHIBITION OF HUMAN P2X(7) PURINOCEPTOR BY 17-BETA-ESTRADIOL

1. Effects of oestrogen on the current evoked by ATP and benzoylbenzoy l ATP (BzATP) in CV-1. monkey kidney cells transformed by SV 40 (COS c ells) expressing the human P2X(7) (hP2X(7)) purinoceptor were studied using standard patch-damp techniques. 2. 17 beta-Oestradiol rapidly an d reversibly inhibited the whole-cell hP2X, receptor cation current. T his inhibitory action resulted in a rightward shift of the dose-respon se curve to ATP and BzATP in the presence of physiological as well as low divalent cation concentrations. 3. The inhibitory effect of 17 bet a-oestradiol on the BzATP- or ATP-induced cation current was concentra tion dependent. The half-maximal inhibition was obtained with 3 mu M 1 7 beta-oestradiol. Progesterone and 17 alpha-oestradiol had almost no effect on the hP2X(7) receptor cation current. 4. The inhibition of th e hP2X(7) receptor cation current by 17 beta-oestradiol did not depend on the membrane potential. 17 beta-Oestradiol added to the extracellu lar side of outside-out patches inhibited BzATP-activated single-chann el currents. 5. Activation of the hP2X(7) receptor in both COS and U93 7 (human macrophage) cells did not induce the formation of large non-s pecific pores. 6. Since COS cells do not express endogenous nuclear oe strogen receptor, this study shows that, at pharmacological concentrat ions, 17 beta-oestradiol inhibited the hP2X(7) receptor cation channel in a non-genomic manner.