Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity
Autor: | Yongmeng Wang, Ruobing Qu, Xinghong Jiang, Liyan Zhu, Liting Zhao, Hong-Yan Zhu, Guang-Yin Xu |
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Rok vydání: | 2015 |
Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Adrenergic beta-Antagonists TRPV1 Cystathionine beta-Synthase TRPV Cation Channels Adrenergic Inflammation Article Tacrolimus Irritable Bowel Syndrome Rats Sprague-Dawley Norepinephrine Dorsal root ganglion Downregulation and upregulation Ganglia Spinal Internal medicine Hypersensitivity medicine Animals Sulfites Receptor Multidisciplinary Behavior Animal biology Chemistry Adrenergic beta-Agonists Propranolol Cystathionine beta synthase Rats Up-Regulation Disease Models Animal medicine.anatomical_structure Endocrinology biology.protein Receptors Adrenergic beta-2 medicine.symptom Signal transduction Signal Transduction |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep16109 |
Popis: | The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by β2 subunit inhibitor but not by β1 or β3 or α subunit inhibitor. NCI markedly elevated plasma norepinephrine (NE) concentration without alteration in expression of β2 subunit receptors in dorsal root ganglion (DRGs) innervating the colon. In addition, NCI markedly enhanced TRPV1 and CBS expression in the colon DRGs. CBS inhibitor AOAA reversed the upregulation of TRPV1 in NCI rats. In vitro experiments showed that incubation of DRG cells with NE markedly enhanced expression of TRPV1, which was reversed by application of AOAA. Incubation of DRG cells with the H2S donor NaHS greatly enhanced TRPV1 expression. Collectively, these data suggest that activation of adrenergic signaling by NCI sensitizes TRPV1 channel activity, which is likely mediated by upregulation of CBS expression in peripheral sensory neurons, thus contributing to chronic visceral hypersensitivity. |
Databáze: | OpenAIRE |
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