title: Interaction between P2X3 and oestrogen receptor (ER)α/ERβ in ATP-mediated calcium signalling in mice sensory neurones.
abstract: Emerging evidence supports a role of purinergic P2X3 receptors in modulating nociceptive signalling in sensory neurones. Previously, we showed that dorsal root ganglion (DRG) neurones (L1-S1) express both oestrogen receptor (ER)α and ERβ receptors. In the present study, we investigated the expression of P2X3 receptors and the effect of 17β-oestradiol (E(2)) on the ATP-induced [Ca(2+)](i) increase in DRG neurones collected from C57Bl/6J, ERα knockout (KO) and ERβKO mice. Our data showed a significant decrease for P2X3 in ERαKO (all levels) and ERβKO (mostly observed in L1, L2, L4 and L6). Furthermore, E(2) (100 nm) significantly attenuated the ATP (10 μm)-induced [Ca(2+)](i) in C57Bl/6J mice. ER antagonist ICI 182,780 (1 μm) blocked this attenuation. Homomeric P2X3 receptors are plentifully expressed in DRG neurones and contribute to nociceptive signals. α,β-Methylene (α,β-me) ATP, which is a specific agonist of P2X2/3 receptors, showed similar responses to the ATP-induced calcium increase in KO mice. A membrane-impermeable E-6-bovine serum albumin (1 μm) had the same effect as E(2) , suggesting action on the membrane. In DRG neurones from ERβKO and wild-type mice, E(2) attenuated the ATP/α,β-me ATP-induced [Ca(2+)](i) fluxes but, in DRG neurones from ERαKO mice, this hormone had no effect, suggesting that this attenuation depends on membrane-associated ERα receptors. Together, our data indicate an interaction between P2X3 and membrane-associated ERα in primary sensory neurones that may represent a novel mechanism to explain sex differences observed in the clinical presentation of visceral nociceptive syndromes.
authors.affiliation: Department of Health Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Cho
authors.forename: V V
authors.initials: VV
authors.lastname: Chaban
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D058477:Receptors, Purinergic P2X3; D004958:Estradiol; D000255:Adenosine Triphosphate; D002118:Calcium