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Inhibition of Protein Kinases AKT and ERK1/2 Reduce the Carotid Body Chemoreceptor Response to Hypoxia in Adult Rats

  • Pablo Iturri
  • Vincent Joseph
  • Gloria Rodrigo
  • Aida Bairam
  • Jorge SolizEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)

Abstract

The carotid body is the main mammalian oxygen-sensing organ regulating ventilation. Despite the carotid body is subjected of extensive anatomical and functional studies, little is yet known about the molecular pathways signaling the neurotransmission and neuromodulation of the chemoreflex activity. As kinases are molecules widely involved in motioning a broad number of neural processes, here we hypothesized that pathways of protein kinase B (AKT) and extracellular signal-regulated kinases ½ (ERK1/2) are implicated in the carotid body response to hypoxia. This hypothesis was tested using the in-vitro carotid body/carotid sinus nerve preparation (“en bloc”) from Sprague Dawley adult rats. Preparations were incubated for 60 min in tyrode perfusion solution (control) or containing 1 μM of LY294002 (AKT inhibitor), or 1 μM of UO-126 (ERK1/2 inhibitor). The carotid sinus nerve chemoreceptor discharge rate was recorded under baseline (perfusion solution bubbled with 5 % CO2 balanced in O2) and hypoxic (perfusion solution bubbled with 5 % CO2 balanced in N2) conditions. Compared to control, both inhibitors significantly decreased the normoxic and hypoxic carotid body chemoreceptor activity. LY294002- reduced carotid sinus nerve discharge rate in hypoxia by about 20 %, while UO-126 reduces the hypoxic response by 45 %. We concluded that both AKT and ERK1/2 pathways are crucial for the carotid body intracellular signaling process in response to hypoxia.

Keywords

Carotid body Hypoxia Chemoreception ERK AKT 

Notes

Acknowledgements

The authors wish to thank to Melanie Pelletier for her superb assistance and Richard Kinkead for fruitful discussions. J.S. is supported by grants from The Molly Towell Perinatal research Foundation (MTPRF), The Fonds de la Recherche Québec en Santé (FRQ-S: MOP-26974), and The Canadian Institute for Health Research (CIHR: MOP-130258).

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Pablo Iturri
    • 1
    • 2
  • Vincent Joseph
    • 1
  • Gloria Rodrigo
    • 2
  • Aida Bairam
    • 3
    • 4
  • Jorge Soliz
    • 1
    Email author
  1. 1.Department of Pediatrics, Centre de Recherche de l’Hôpital St-François d’Assise (CR-SFA), Faculty of MedicineCentre Hospitalier Universitaire de Québec (CHUQ), Laval UniversityQuébecCanada
  2. 2.Molecular Biology and Biotechnology InstituteUniversidad Mayor de San AndresLa PazBolivia
  3. 3.Pediatric Department, Laval University, Research Center of Centre HospitalierUniversitaire de QuebecQuebec CityCanada
  4. 4.Centre de recherche du CHUQHSFAQuébecCanada

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