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

• Published in: The Journal of physiology Vol. 508; no. 3; pp. 659 - 666
• Main Authors: Cario‐Toumaniantz, Chrystelle, Loirand, Gervaise, Ferrier, Laurent, Pacaud, Pierre
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.1998; Blackwell Science Inc
• Subjects: Rapid Report
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1998.659bp.x

1 Effects of oestrogen on the current evoked by ATP and benzoylbenzoyl ATP (BzATP) in CV‐1 monkey kidney cells transformed by SV 40 (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.