title: Somatostatin modulates generation of inspiratory rhythms and determines asphyxia survival.
abstract: Breathing and the activity of its generator (the pre-Bötzinger complex; pre-BötC) are highly regulated functions. Among neuromodulators of breathing, somatostatin (SST) is unique: it is synthesized by a subset of glutamatergic pre-BötC 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 preBötC-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-Bötzinger 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.
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, UNAM-Campus Juriquilla, Mexico. josue8orlando@yahoo.com.mx
authors.forename: Josué O
authors.initials: JO
authors.lastname: Ramírez-Jarquín
authors.forename: Sergio
authors.initials: S
authors.lastname: Lara-Hernández
authors.forename: Juan J
authors.initials: JJ
authors.lastname: López-Guerrero
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Aguileta
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Rivera-Angulo
authors.forename: Alicia
authors.initials: A
authors.lastname: Sampieri
authors.forename: Luis
authors.initials: L
authors.lastname: Vaca
authors.forename: Benito
authors.initials: B
authors.lastname: Ordaz
authors.forename: Fernando
authors.initials: F
authors.lastname: Peña-Ortega
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D055724:Electrophysiological Phenomena; D000860:Hypoxia / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D001239:Inhalation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology* / Q000502:physiology; D010507:Periodicity; D010991:Plethysmography; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics; D012125:Respiratory Center / Q000187:drug effects* / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology* / Q000502:physiology; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D018377:Neurotransmitter Agents; D017481:Receptors, Somatostatin; C570769:somatostatin receptor 2, mouse; D013004:Somatostatin