EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B

Hsi-Chin Wu, Chao-Hsiang Chang, Hsien-Yu Peng, Gin-Den Chen, Cheng-Yuang Lai, Ming-Chun Hsieh, Tzer-Bin Lin
2011 AJP - Renal Physiology  
respective cells and vasculature, as well as to the control of body fluid volume and composition. It is published 12 times a year publishes original manuscripts on a broad range of subjects relating to the kidney, urinary tract, and their AJP -Renal Physiology Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in painrelated neural plasticity at the spinal cord level have been identified. To test whether Src-family tyrosine kinase-dependent glutamatergic
more » ... yl-D-aspartate receptor NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate pelvic-urethra reflex potentiation, we recorded external urethra sphincter electromyogram reflex activity and analyzed protein expression in the lumbosacral (L6-S2) dorsal horn in response to intrathecal ephrinB2 injections. When compared with vehicle solution, exogenous eph-rinB2 (5 g/rat it)-induced reflex potentiation, in associated with phosphorylation of EphB1/2, Src-family kinase, NR2B Y1336 and Y1472 tyrosine residues. Both intrathecal EphB1 and EphB2 immunoglobulin fusion protein (both 10 g/rat it) prevented ephrinB2dependent reflex potentiation, as well as protein phosphorylation. Pretreatment with PP2 (50 M, 10 l it), an Src-family kinase antagonist, reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation. Together, these results suggest the ephrinB2dependent EphBR activation, which subsequently provokes Src kinase-mediated N-methyl-D-aspartate receptor NR2B phosphorylation in the lumbosacral dorsal horn, is crucial for the induction of spinal reflex potentiation contributing to the development of visceral pain and/or hyperalgesia in the pelvic area. pelvic pain; urethra; Src-family kinase; N-methyl-D-aspartate
doi:10.1152/ajprenal.00520.2010 pmid:21147838 fatcat:g2okhqofincnlkzzkd22kzz27e