Advertisement

Adenosine Mediates Hypercapnic Response in the Rat Carotid Body via A2A and A2B Receptors

  • Joana F. Sacramento
  • Bernardete F. Melo
  • Sílvia V. CondeEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1071)

Abstract

Adenosine is one of the key neurotransmitters involved in hypoxic signaling in the carotid body (CB), and it was recently found to have a modulatory role in mediating hypercapnic sensitivity in the CB. Herein we have investigated the contribution of adenosine to the hypercapnic response in the rat CB and studied the adenosine receptors responsible for this effect. Experiments were performed in Wistar rats. Adenosine release in normoxia (21% O2) and in response to hypercapnia (10% CO2) was quantified by HPLC. Carotid sinus nerve (CSN) chemosensory activity was evaluated in response to hypercapnia in the absence and presence of ZM241385 (300 nM), an A2 antagonist, and SCH58261 (20 nM), a selective A2A antagonist. Hypercapnia increased the extracellular concentrations of adenosine by 50.01%. Both, ZM241385 and SCH58261, did not modify significantly the basal frequency of discharges of the CSN. Also, ZM241385 and SCH58261 did not modify the latency time and the time to peak in CSN chemosensory activity. CSN activity evoked by hypercapnia decreased by 58.82 and 33.59% in response to ZM241385 and to SCH58261, respectively. In conclusion, the effect of adenosine in mediating the hypercapnic response in the rat CB involves an effect on A2A and A2B adenosine receptors.

Keywords

Adenosine Adenosine receptors Carotid body Carotid sinus nerve activity Hypercapnia 

Notes

Acknowledgements

J.F.S. and B.F.M. are supported by PhD Grants from Portuguese Foundation for Science and Technology Reference PD/BD/105890/2014 and PD/BD/128336/2017, respectively.

References

  1. Blain GM, Smith CA, Henderson KS, Dempsey JA (2010) Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2. J Physiol 588:2455–2471CrossRefGoogle Scholar
  2. Conde SV, Monteiro EC (2004) Hypoxia induces adenosine release from the rat carotid body. J Neurochem 89:1148–1156CrossRefGoogle Scholar
  3. Conde SV, Obeso A, Vicario I, Rigual R, Rocher A, Gonzalez C (2006) Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors. J Neurochem 98:616–628CrossRefGoogle Scholar
  4. Conde SV, Monteiro EC, Obeso A, Gonzalez C (2009) Adenosine in peripheral chemoreception: new insights into a historically overlooked molecule. Adv Exp Med Biol 648:159–174Google Scholar
  5. Conde SV, Monteiro EC, Rigual R, Obeso A, Gonzalez C (2012) Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensoryactivity. J Appl Physiol 112:2002–2010CrossRefGoogle Scholar
  6. Gonzalez C, Almaraz L, Obeso A, Rigual R (1994) Carotid body chemoreceptors: from natural stimuli to sensory discharges. Physiol Rev 74:829–898CrossRefGoogle Scholar
  7. Heeringa J, Berkenbosch A, de Goede J, Olievier CN (1979) Relative contribution of central and peripheral chemoreceptors to the ventilatory response to CO2 during hyperoxia. Respir Physiol 37:365–379CrossRefGoogle Scholar
  8. Holmes AP, Nunes AR, Cann MJ, Kumar P (2015) Ecto-5′-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia. Adv Exp Med Biol 860:279–289CrossRefGoogle Scholar
  9. Nattie E (1999) CO2, brainstem chemoreceptors and breathing. Prog Neurobiol 59:299–331CrossRefGoogle Scholar
  10. Rigual R, Rico AJ, Prieto-Lloret J, de Felipe C, Gonzalez C, Donnelly DF (2002) Chemoreceptor activity is normal in mice lacking the NK1 receptor. Eur J Neurosci 16:2078–2084CrossRefGoogle Scholar
  11. Rodman JR, Curran AK, Henderson KS, Dempsey JA, Smith CA. (2001) Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia. J Appl Physiol 91(1):328–35CrossRefGoogle Scholar
  12. Sebastião AM, Ribeiro JA (2009) Tuning and fine-tuning of synapses with adenosine. Curr Neuropharmacol 7(3):180–94CrossRefGoogle Scholar
  13. Smith CA, Blain GM, Henderson KS, Dempsey JA (2015) Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2: role of carotid body CO2. J Physiol 593:4225–4243CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Joana F. Sacramento
    • 1
  • Bernardete F. Melo
    • 1
  • Sílvia V. Conde
    • 1
    Email author
  1. 1.CEDOC, Centro de Estudos Doenças Crónicas, Nova Medical School, Faculdade de Ciências MédicasUniversidade Nova de LisboaLisbonPortugal

Personalised recommendations