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

Research output: Contribution to journalArticle

18 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

Fingerprint

src-Family Kinases
Eph Family Receptors
Urethra
Colon
Phosphorylation
Protein-Tyrosine Kinases
EphB2 Receptors
Reflex
Visceral Pain
Referred Pain
Neuronal Plasticity
Electromyography
Immunoglobulins
Spinal Cord
Up-Regulation
Ligands
Pain
mustard oil
Proteins
NR2B NMDA receptor

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology
  • Medicine(all)

Cite this

Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B. / Peng, Hsien Yu; Chen, Gin Den; Lai, Cheng Hung; Tung, Kwong Chung; Chang, Junn Liang; Lin, Tzer Bin.

In: American Journal of Physiology - Renal Physiology, Vol. 298, No. 1, 01.2010.

Research output: Contribution to journalArticle

@article{7d00b24ef5b646c1ace755dfb5a4dba6,
title = "Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B",
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.",
keywords = "Colon, Irritable bowel syndrome, NMDA, Pelvic pain syndrome, Urethra",
author = "Peng, {Hsien Yu} and Chen, {Gin Den} and Lai, {Cheng Hung} and Tung, {Kwong Chung} and Chang, {Junn Liang} and Lin, {Tzer Bin}",
year = "2010",
month = "1",
doi = "10.1152/ajprenal.00287.2009",
language = "English",
volume = "298",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B

AU - Peng, Hsien Yu

AU - Chen, Gin Den

AU - Lai, Cheng Hung

AU - Tung, Kwong Chung

AU - Chang, Junn Liang

AU - Lin, Tzer Bin

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

KW - Colon

KW - Irritable bowel syndrome

KW - NMDA

KW - Pelvic pain syndrome

KW - Urethra

UR - http://www.scopus.com/inward/record.url?scp=74049103334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74049103334&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00287.2009

DO - 10.1152/ajprenal.00287.2009

M3 - Article

VL - 298

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1931-857X

IS - 1

ER -