Modulation of hypercapnic respiratory response by cholinergic transmission in the commissural nucleus of the solitary tract

  • Werner I. Furuya
  • Mirian Bassi
  • José V. Menani
  • Eduardo Colombari
  • Daniel B. Zoccal
  • Débora S. A. ColombariEmail author
Integrative physiology
Part of the following topical collections:
  1. Integrative Physiology


The nucleus of the solitary tract (NTS) is an important area of the brainstem that receives and integrates afferent cardiorespiratory sensorial information, including those from arterial chemoreceptors and baroreceptors. It was described that acetylcholine (ACh) in the commissural subnucleus of the NTS (cNTS) promotes an increase in the phrenic nerve activity (PNA) and antagonism of nicotinic receptors in the same region reduces the magnitude of tachypneic response to peripheral chemoreceptor stimulation, suggesting a functional role of cholinergic transmission within the cNTS in the chemosensory control of respiratory activity. In the present study, we investigated whether cholinergic receptor antagonism in the cNTS modifies the sympathetic and respiratory reflex responses to hypercapnia. Using an arterially perfused in situ preparation of juvenile male Holtzman rats, we found that the nicotinic antagonist (mecamylamine, 5 mM), but not the muscarinic antagonist (atropine, 5 mM), into the cNTS attenuated the hypercapnia-induced increase of hypoglossal activity. Furthermore, mecamylamine in the cNTS potentiated the generation of late-expiratory (late-E) activity in abdominal nerve induced by hypercapnia. None of the cholinergic antagonists microinjected in the cNTS changed either the sympathetic or the phrenic nerve responses to hypercapnia. Our data provide evidence for the role of cholinergic transmission in the cNTS, acting on nicotinic receptors, modulating the hypoglossal and abdominal responses to hypercapnia.


Hypercapnia Nicotinic receptors Muscarinic receptors Acetylcholine Brainstem Chemoreflex 


Author contributions

Furuya WI performed all the experiments, analyzed data, and wrote the paper. Colombari DSA and Zoccal DB designed the experiments, analyzed the data, and wrote the paper. Colombari E, Bassi M, and Menani JV analyzed the data and revised manuscript.

Funding information

This research was supported by Conselho Nacional de Pesquisa (CNPq 425,586/2016–2; 304,873/2014–4; 408,950/2018–8, 310,331/2017–0), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2013/22526–4, 2013/17251–6, and 2015/234677), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Finance Code 001). This work is part of the requirements to obtain a PhD degree by Werner I. Furuya in the Joint Graduate Program in Physiological Sciences PIPGCF UFSCar/UNESP.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

424_2019_2341_MOESM1_ESM.pdf (336 kb)
ESM 1 (PDF 335 kb).


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Physiology and Pathology, School of DentistryUNESP - São Paulo State UniversityAraraquaraBrazil

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