Somatostatin modulates generation of inspiratory rhythms and determines asphyxia survival

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• 作者：Josué ; O. Ramí ; rez-Jarquí ; n^a ; ^b ; ^{josue8orlando@yahoo.com.mx} ; Sergio Lara-Herná ; ndez^b ; ^{slarah29@gmail.com} ; Juan J. L&#243 ; pez-Guerrero^b ; ^{jjavierlg@hotmail.com} ; Miguel A. Aguileta^a ; ^{miguelaguileta@gmail.com} ; Ana J. Rivera-Angulo^a ; ^{ana_jra3@hotmail.com} ; Alicia Sampieri^c ; ^{asampier@ifc.unam.mx} ; Luis Vaca^c ; ^{lvaca@ifc.unam.mx} ; Benito Ordaz^a ; ^{jrseau55@hotmail.com} ; Fernando Peñ ; a-Ortega^a ; ^{jfpena@unam.mx}
• 关键词：CNS ; central nervous system ; pre-Bö ; tC ; pre-Bö ; tzinger complex ; SST ; somatostatin ; SSTRs ; somatostatin receptors ; SSTR2 ; somatostatin receptor type 2 ; ACSF ; artificial cerebrospinal fluid ; qPCR ; quantitative real time PCR ; BIM23014C ; 尾-(2-naphthy
• 刊名：Peptides
• 出版年：2012
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：April, 2012
• 卷：34
• 期：2
• 页码：360-372
• 文件大小：2272 K

摘要

Breathing and the activity of its generator (the pre-B枚tzinger complex; pre-B枚tC) are highly regulated functions. Among neuromodulators of breathing, somatostatin (SST) is unique: it is synthesized by a subset of glutamatergic pre-B枚tC neurons, but acts as an inhibitory neuromodulator. Moreover, SST regulates breathing both in normoxic and in hypoxic conditions. Although it has been implicated in the neuromodulation of breathing, neither the locus of SST modulation, nor the receptor subtypes involved have been identified. In this study, we aimed to fill in these blanks by characterizing the SST-induced regulation of inspiratory rhythm generation in vitro and in vivo. We found that both endogenous and exogenous SST depress all preB枚tC-generated rhythms. While SST abolishes sighs, it also decreases the frequency and increases the regularity of eupnea and gasping. Pharmacological experiments showed that SST modulates inspiratory rhythm generation by activating SST receptor type-2, whose mRNA is abundantly expressed in the pre-B枚tzinger complex. In vivo, blockade of SST receptor type-2 reduces gasping amplitude and consequently, it precludes auto-resuscitation after asphyxia. Based on our findings, we suggest that SST functions as an inhibitory neuromodulator released by excitatory respiratory neurons when they become overactivated in order to stabilize breathing rhythmicity in normoxic and hypoxic conditions.