title: Corticotropin-releasing factor in the locus coeruleus as a modulator of ventilation in rats.
abstract: The locus coeruleus (LC) is a pontine noradrenergic nucleus that acts as a central chemoreceptor to CO2/pH and has been implicated in the cognitive aspects of stress responses. This participation is in part mediated by the action of corticotropin-releasing factor (CRF), which when released in these situations increases the firing frequency of LC noradrenergic neurons. Nevertheless, the role of CRF1receptors in the LC in breathing and temperature control is unknown. Therefore, we tested the involvement of CRF1receptors located in the LC in room air ventilation and the ventilatory response induced by hypercapnia (7% CO2) in rats. To this end, we injected CRF-R1-selective antagonists (antalarmin-1.2 and 2.4mmol/0.1μL or CP-376395-5nmol/0.1μL) into the LC of male Wistar rats. Pulmonary ventilation (VE) and body temperature (Tb, dataloggers) were measured in air, followed by 7% CO2in unanesthetized rats. Antalarmin (higher dose) and CP-376395 in the LC caused an increase in VEduring normocapnia and hypercapnia, due to an increase in tidal volume. There were no differences in Tb between groups under normocapnia and hypercapnia. The results suggest that CRF acting on CRF1receptors in the LC exerts a tonic inhibitory role in ventilation.
authors.affiliation: Departamento de Morfologia e Fisiologia Animal, Faculdade de Ciências Agrárias e Veterinárias-UNESP, Jaboticabal, Brazil; National Institute of Science and Technology in Comparative Physiology (INCT Fisiologia Comparada), Brazil.
authors.forename: Jolene M
authors.initials: JM
authors.lastname: Incheglu
authors.affiliation: Departamento de Morfologia e Fisiologia Animal, Faculdade de Ciências Agrárias e Veterinárias-UNESP, Jaboticabal, Brazil; National Institute of Science and Technology in Comparative Physiology (INCT Fisiologia Comparada), Brazil.
authors.forename: Kênia Cardoso
authors.initials: KC
authors.lastname: Bícego
authors.affiliation: Departamento de Morfologia e Fisiologia Animal, Faculdade de Ciências Agrárias e Veterinárias-UNESP, Jaboticabal, Brazil; National Institute of Science and Technology in Comparative Physiology (INCT Fisiologia Comparada), Brazil. Electronic address: lucihel@fcav.unesp.br.
authors.forename: Luciane H
authors.initials: LH
authors.lastname: Gargaglioni
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006935:Hypercapnia / Q000503:physiopathology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology
chemical_list: C529296:(3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine; D000631:Aminopyridines; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D003346:Corticotropin-Releasing Hormone
keywords: CRF receptors; Chemoreception; Hypercapnia; Locus coeruleus; Ventilation