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Interaction Between P2X3 and Oestrogen Receptor (ER)α/ERβ in ATP‐Mediated Calcium Signalling In Mice Sensory Neurones
Author(s) -
Cho T.,
Chaban V. V.
Publication year - 2012
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2011.02272.x
Subject(s) - receptor , medicine , dorsal root ganglion , endocrinology , purinergic receptor , homomeric , chemistry , agonist , calcium imaging , calcium , biology , sensory system , biochemistry , neuroscience , protein subunit , gene
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 n m ) significantly attenuated the ATP (10 μ m )‐induced [Ca 2+ ] i in C57Bl/6J mice. ER antagonist ICI 182,780 (1 μ m ) 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 μ m ) 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.