title: Effect of Systemic Application of 5-Hydroxytryptamine on Hypoglossal Nerve Discharge in Anesthetized Rats.
abstract: The aim of this study is to investigate whether systemic 5-hydroxytryptamine (5-HT) can promote long-lasting form of respiratory plasticity in vivo via 5-HT2AR-activated protein kinase C (PKC) mechanism. The frequency and peak amplitude of hypoglossal nerve discharges in anesthetized rats were compared before and after intravenous injections of different treatments, including saline, 5-HT, ketanserin tartrate, or staurosporine. The administration of 5-HT at a systemic bolus imposed an initial ephemeral inhibition subsequently followed by striking facilitation, which demonstrates a biphasic manner of hypoglossal nerve output in anesthetized adult rats. The facilitatory stage conformed to the reinforced hypoglossal activity that lasted for more than 60 min after drug administration. The 5-HT evoked biphasic manner of hypoglossal output and hypoglossal nerve activity LTF (hLTF) were 5-HT2A receptor-dependent and coupled to PKC activation. The initial inhibition of hypoglossal activity was associated with nodose ganglion, and the subsequent facilitation was associated with carotid body. The reactive oxygen species (ROS) formation was triggered in the systemic 5-HT2-dependent hLTF model in vivo. The expressions of immunofluorescent histochemistry provide morphological evidence of a 5-HT/5-HT2A receptor coupled to PKC mechanism. In conclusion, systemic 5-HT challenge contributes to long-lasting form of respiratory plasticity and to elicit hLTF or elevated hLTF in animals, which with decreased or even with inhibited peripheral inhibitory activations. The effect of systemic 5-HT was regulated by a 5-HT2AR-activated PKC mechanism.
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Tu
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Zuo
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China. huke_rmhospital@yeah.net.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kang
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Yongtian
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000768:Anesthesia, General; D000818:Animals; D002344:Carotid Body / Q000201:enzymology / Q000502:physiology; D007002:Hypoglossal Nerve / Q000187:drug effects* / Q000502:physiology; D007275:Injections, Intravenous; D007650:Ketanserin / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology; D009620:Nodose Ganglion / Q000201:enzymology / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D019311:Staurosporine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012701:Serotonin; D007650:Ketanserin; D011493:Protein Kinase C; D019311:Staurosporine
keywords: Hypoglossal nerve; Long-term facilitation; Protein kinase C; Respiratory neuroplasticity; Serotonin