title: Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Neurobiology and Physiology, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Neurobiology and Physiology, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Liting
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Neurobiology and Physiology, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Qu
authors.affiliation: Center for Translational Medicine, the Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, 215600, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Neurobiology and Physiology, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Yongmeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Neurobiology and Physiology, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Neurobiology and Physiology, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.|Center for Translational Medicine, the Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, 215600, P.R. China.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000473:pathology; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013447:Sulfites / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C112418:32-ascomycinyloxyacetic acid; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D013447:Sulfites; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C569244:sodium hydrogen sulfite; D011433:Propranolol; D003541:Cystathionine beta-Synthase; D016559:Tacrolimus; D009638:Norepinephrine