Estradiol attenuates the adenosine triphosphate-induced increase of intracellular calcium through group II metabotropic glutamate receptors in rat dorsal root ganglion neurons.

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.