Non-genomic inhibition of human P2X7 purinoceptor by 17β-oestradiol

Abstract

1. Effects of oestrogen on the current evoked by ATP and benzoylbenzoyl ATP (BzATP) in CV-1 monkey kidney cells transformed by SV40 (COS cells) expressing the human P2X7 (hP2X7) purinoceptor were studied using standard patch-clamp techniques. 2. 17β-Oestradiol rapidly and reversibly inhibited the whole-cell hP2X7 receptor cation current. This inhibitory action resulted in a rightward shift of the dose-response curve to ATP and BzATP in the presence of physiological as well as low divalent cation concentrations. 3. The inhibitory effect of 17β-oestradiol on the BzATP- or ATP-induced cation current was concentration dependent. The half-maximal inhibition was obtained with 3 μM 17β-oestradiol. Progesterone and 17α-oestradiol had almost no effect on the hP2X7 receptor cation current. 4. The inhibition of the hP2X7 receptor cation current by 17β-oestradiol did not depend on the membrane potential. 17β-Oestradiol added to the extracellular side of outside-out patches inhibited BzATP-activated single-channel currents. 5. Activation of the hP2X7 receptor in both COS and U937 (human macrophage) cells did not induce the formation of large non-specific pores. 6. Since COS cells do not express endogenous nuclear oestrogen receptor, this study shows that, at pharmacological concentrations, 17β-oestradiol inhibited the hP2X7 receptor cation channel in a non-genomic manner.