Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B

Hsien Yu Peng, Gin Den Chen, Cheng Hung Lai, Kwong Chung Tung, Junn Liang Chang, Tzer Bin Lin

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20 Citations (Scopus)

Abstract

Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in spinal pain-related neural plasticity has been identified. To test whether Src-family non-receptor tyrosine kinase-dependent glutamatergic N-methyl-D-aspartate receptor (NMDAR) NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate crossorgan sensitization between the colon and the urethra, external urethra sphincter electromyogram activity evoked by pelvic nerve stimulation and protein expression in the lumbosacral (L6-S2) dorsal horn were studied before and after intracolonic mustard oil (MO) instillation. We found MO instillation produced colon-urethra reflex sensitization along with an upregulation of endogenous ephrinB2 expression as well as phosphorylation of EphB1/2, Src-family kinase, and NR2B tyrosine residues. Intrathecal immunoglobulin fusion protein of EphB1 and EphB2 as well as PP2 reversed the reflex sensitization and NR2B phosphorylation caused by MO. All these results suggest that EphBR-ephrinB interactions, which provoke Src-family kinase-dependent NMDAR NR2B phosphorylation at the lumbosacral spinal cord level, are involved in cross-organ sensitization, contributing to the development of viscero-visceral referred pain between the bowel and the urethra.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume298
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

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Keywords

  • Colon
  • Irritable bowel syndrome
  • NMDA
  • Pelvic pain syndrome
  • Urethra

ASJC Scopus subject areas

  • Physiology
  • Urology
  • Medicine(all)

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