科研之友
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摘要
Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE) plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores (AWRs) used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs) were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of beta(2)-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a beta-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a alpha-adrenoceptor antagonist phentolamine. Using specific beta-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by beta(2) adrenoceptor antagonist but not by beta(1)-or beta(3)-adrenoceptor antagonist. Administration of a selective beta(2)-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of beta-adrenoceptor antagonist suppressed sustained potassium current density (I-K) without any alteration of fast-inactivating potassium current density (I-A). Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by beta(2)-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of beta(2)-adrenoceptor in DRGs and the muscularis externa of the colon. The present study might provide a potential molecular target for therapy of visceral hypersensitivity in patents with IBS.
- 出版日期2014-4-14
- 单位苏州大学
