Non-genomic inhibition of human P2X7 purinoceptor by 17beta-oestradiol.
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. 17beta-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 17beta-oestradiol on the BzATP- or ATP-induced cation current was concentration dependent. The half-maximal inhibition was obtained with 3 microM 17beta-oestradiol. Progesterone and 17alpha-oestradiol had almost no effect on the hP2X7 receptor cation current. 4. The inhibition of the hP2X7 receptor cation current by 17beta-oestradiol did not depend on the membrane potential. 17beta-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, 17beta-oestradiol inhibited the hP2X7 receptor cation channel in a non-genomic manner.
Cario-Toumaniantz
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C
Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UPR 411, 660 route des lucioles, Sophia Antipolis, 06560 Valbonne, France.
Loirand
G
G
Ferrier
L
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Pacaud
P
P
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D019556:COS Cells / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004996:Ethidium / Q000493:pharmacokinetics; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008593:Menopause; D018408:Patch-Clamp Techniques; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*
D000345:Affinity Labels; D002412:Cations; D004791:Enzyme Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D004958:Estradiol; D000255:Adenosine Triphosphate; D004996:Ethidium; D008274:Magnesium; D002118:Calcium