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.