title: Estradiol attenuates the adenosine triphosphate-induced increase of intracellular calcium through group II metabotropic glutamate receptors in rat dorsal root ganglion neurons.
abstract: Estradiol attenuates the ATP-induced increase of intracellular calcium concentration ([Ca(2+)](i)) in rat dorsal root ganglion (DRG) neurons by blocking the L-type voltage gated calcium channel (VGCC). Because ATP is a putative nociceptive signal, this action may indicate a site of estradiol regulation of pain. In other neurons, 17β-estradiol (E(2)) has been shown to modulate L-type VGCC through a membrane estrogen receptor-group II metabotropic glutamate receptor (mGluR(2/3)). The present study investigated whether the rapid estradiol attenuation of the ATP-induced increase in [Ca(2+)](i) requires mGluR(2/3). Previously we showed that DRG (L(1)-S(3)) express ERα, P2X(3), and mGluR(2/3) receptors. DRG were acutely dissociated by enzyme digestion and grown in short-term culture for imaging analysis. DRG neurons were stimulated twice, once with ATP (50 μM) for 5 sec and then again in the presence of E(2) (100 nM) or E(2) (100 nM) + LY341495 (100 nM), an mGluR(2/3) inhibitor. ATP induced a transient increase in [Ca(2+)](i) (216.3 ± 41.2 nM). This transient increase could be evoked several times in the same DRG neurons if separated by a 5-min washout. Treatment with estradiol significantly attenuated the ATP-induced [Ca(2+)](i) increase in 60% of the DRG neurons, to 163.3 ± 20.9 nM (P < 0.001). Coapplication of E(2) and the mGluR(2/3) inhibitor LY341495 blocked the 17β-estradiol attenuation of the ATP-induced [Ca(2+) ](i) transient (209.1 ± 32.2 nM, P > 0.05). These data indicate that the rapid action of E(2) in DRG neurons is dependent on mGluR(2/3) and demonstrate that membrane estrogen receptor-α-initiated signaling involves interaction with mGluRs.
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California, USA. victorchaban@cdrewu.edu
authors.forename: Victor
authors.initials: V
authors.lastname: Chaban
authors.forename: Jichang
authors.initials: J
authors.lastname: Li
authors.forename: John S
authors.initials: JS
authors.lastname: McDonald
authors.forename: Andrea
authors.initials: A
authors.lastname: Rapkin
authors.forename: Paul
authors.initials: P
authors.lastname: Micevych
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011960:Receptors, Estrogen / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D004967:Estrogens; C114624:LY 341495; D011960:Receptors, Estrogen; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D004958:Estradiol; D000255:Adenosine Triphosphate; D002118:Calcium