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GPR30 estrogen receptor agonists induce mechanical hyperalgesia in the rat

MPS-Authors

Kuhn,  Julia
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50170

Goswami,  Chandan
Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50579

Suckow,  Vanessa
Signal Transduction in Mental Retardation and Pain (Tim Hucho), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50297

Hucho,  Tim
Signal Transduction in Mental Retardation and Pain (Tim Hucho), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Kuhn, J., Dina, O. A., Goswami, C., Suckow, V., Levine, J. D., & Hucho, T. (2008). GPR30 estrogen receptor agonists induce mechanical hyperalgesia in the rat. European Journal of Neuroscience, 27(7), 1700-1709. doi:10.1111/j.1460-9568.2008.06131.x.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-806F-6
Abstract
We evaluated the signalling pathway by which estrogen acts in peripheral tissue to produce protein kinase Cepsilon (PKCepsilon)-dependent mechanical hyperalgesia. Specific agonists for the classical estrogen receptors (ER), ERalpha and ERbeta, did not result in activation of PKCepsilon in neurons of dissociated rat dorsal root ganglia. In contrast, G-1, a specific agonist of the recently identified G-protein-coupled estrogen receptor, GPR30, induced PKCepsilon translocation. Involvement of GPR30 and independence of ERalpha and ERbeta was confirmed using the GPR30 agonist and simultaneous ERalpha and ERbeta antagonist ICI 182,780 (fulvestrant). The GPR30 transcript could be amplified from dorsal root ganglia tissue. We found estrogen-induced as well as GPR30-agonist-induced PKCepsilon translocation to be restricted to the subgroup of nociceptive neurons positive for isolectin IB4 from Bandeiraea simplicifolia. Corroborating the cellular results, both GPR30 agonists, G-1 as well as ICI 182,780, resulted in the onset of PKCepsilon-dependent mechanical hyperalgesia if injected into paws of adult rats. We therefore suggest that estrogen acts acutely at GPR30 in nociceptors to produce mechanical hyperalgesia.