PI3K modulates estrogen-dependent facilitation of colon-to-urethra cross-organ reflex sensitization in ovariectomized female rats

Hsien Yu Peng, Gin Den Chen, Cheng Yuan Lai, Ming Chun Hsieh, Hsao Hsun Hsu, Hsi Chin Wu, Tzer Bin Lin

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

To determine the role of 17β-estradiol and involvement of intracellular phosphatidylinositol-3-kinase signaling in cross-organ sensitization between the descending colon and the urethra, we analyzed urethra reflex activity and protein expressions in lumbosacral (L6-S2) spinal dorsal horn in response to mustard oil instillation into the descending colon in ovariectomized female rats. When compared with vehicle solution, intracolonic mustard oil sensitized the NMDA receptor NR2B subunit-dependent reflex activity and increased expression levels of phosphorylated Akt (pAkt) and phosphorylated NR2B (pNR2B) in dorsal horn. Facilitation of reflex sensitization and increases in protein expressions of pAkt and pNR2B in dorsal horn were induced after pre-treatment with a subcutaneous injection of 17β-estradiol (5 μg/kg), 6 h ahead of time, when compared with vehicle solution. This phenomenon was reversed both by intrathecal pre-treatment with ICI 182780 (0.25 mg/kg, i.t.) and LY294002 (50 mg/kg, i.t.). Immunoprecipitation of dorsal horn tissue revealed a protein-protein interaction between pAkt and pNR2B increases, 6 h following the subcutaneous 17β-estradiol when compared with vehicle injections. Results indicate 17β-estradiol may activate the phosphatidylinositol-3-kinase cascade, which subsequently phosphorylates the NR2B subunit, via spinal estrogen receptors ERα/ERβ, to facilitate NMDA-dependent cross-organ sensitization, which is presumed to underlie pelvic viscero-visceral referred pain.

Original languageEnglish
Pages (from-to)54-66
Number of pages13
JournalJournal of Neurochemistry
Volume113
Issue number1
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Fingerprint

Urethra
Phosphatidylinositol 3-Kinases
Reflex
Rats
Estradiol
Estrogens
Colon
Phosphatidylinositol 3-Kinase
Descending Colon
Proteins
Visceral Pain
Referred Pain
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
N-Methylaspartate
Subcutaneous Injections
Immunoprecipitation
Estrogen Receptors
Tissue
Injections
Spinal Cord Dorsal Horn

Keywords

  • Central sensitization
  • Colon
  • Irritable bowel syndrome
  • Pelvic pain syndrome
  • Urethra

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

PI3K modulates estrogen-dependent facilitation of colon-to-urethra cross-organ reflex sensitization in ovariectomized female rats. / Peng, Hsien Yu; Chen, Gin Den; Lai, Cheng Yuan; Hsieh, Ming Chun; Hsu, Hsao Hsun; Wu, Hsi Chin; Lin, Tzer Bin.

In: Journal of Neurochemistry, Vol. 113, No. 1, 04.2010, p. 54-66.

Research output: Contribution to journalArticle

Peng, Hsien Yu ; Chen, Gin Den ; Lai, Cheng Yuan ; Hsieh, Ming Chun ; Hsu, Hsao Hsun ; Wu, Hsi Chin ; Lin, Tzer Bin. / PI3K modulates estrogen-dependent facilitation of colon-to-urethra cross-organ reflex sensitization in ovariectomized female rats. In: Journal of Neurochemistry. 2010 ; Vol. 113, No. 1. pp. 54-66.
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