Glutamate-mediated spinal reflex potentiation involves ERK 1/2 phosphorylation in anesthetized rats

Hsien Yu Peng, Ya Wen Cheng, Shin Da Lee, Yen Chun Ho, Dylan Chou, Gin Den Chen, Chen Li Cheng, Tien Huan Hsu, Kwong Chung Tung, Tzer Bin Lin

研究成果: 雜誌貢獻文章同行評審

16 引文 斯高帕斯(Scopus)

摘要

The extracellular signal-regulated kinase (ERK) cascades are suggested to contribute to excitatory plasticity in the CNS, including the spinal cord. This study investigated whether the ERK involves in the repetitive stimulation-induced spinal reflex potentiation (SRP) in the pelvic nerve-to-external urethra sphincter reflex activities. External urethra sphincter electromyogram in response to pelvic afferent nerve test stimulation (TS, 1/30 Hz) or repetitive stimulation (RS, 1 Hz) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP in associated with significant ERK 1/2 phosphorylation. RS-induced SRP and ERK 1/2 phosphorylation were both abolished by pretreatment of U0126 (MEK inhibitor). Intrathecal CNQX (AMPA receptor antagonist) attenuated, while AP5 (NMDA receptor antagonist) abolished the RS-induced SRP and ERK 1/2 phosphorylation. Pretreated U0126 abolished the SRP elicited by glutamatergic agonists including glutamate, NMDA and AMPA. Intrathecal H89 and BIS7 (PKA and PKC inhibitors, respectively) both abolished the RS- and glutamate agonist-induced SRP as well as ERK 1/2 phosphorylation. In addition, forskolin and PMA (PKA and PKC activator, respectively) induced SRP, which were both abolished by pretreated U0126. Saline distension, mimicking the storage phase of the urinary bladder, induced SRP and ERK 1/2 phosphorylation. In conclusion, activated ERK 1/2 may produce SRP in the pelvic nerve-to-external urethra sphincter reflex activity, which is essential for urine continence. In addition, blockage of spinal ERK 1/2 activation decreases the physiological function of the urethra, indicating that phosphorylation of the ERK 1/2 cascade may represent a novel target for the treatment of patients with neurological incontinence of spinal origin.
原文英語
頁(從 - 到)686-698
頁數13
期刊Neuropharmacology
54
發行號4
DOIs
出版狀態已發佈 - 三月 2008
對外發佈Yes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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