Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors

Research output: Contribution to journalArticlepeer-review

Authors

  • Ana R Nunes
  • Vedangi Sample
  • Martin J Cann
  • Emília C Monteiro
  • Jin Zhang
  • Estelle B Gauda

Abstract

Stimulation of the carotid body (CB) chemoreceptors by hypercapnia triggers a reflex ventilatory response via a cascade of cellular events, which includes generation of cAMP. However, it is not known if molecular CO2/HCO3(-) and/or H(+) mediate this effect and how these molecules contribute to cAMP production. We previously reported that the CB highly expresses HCO3(-)-sensitive soluble adenylyl cyclase (sAC). In the present study we systematically characterize the role of sAC in the CB, comparing the effect of isohydric hypercapnia (IH) in cAMP generation through activation of sAC or transmembrane-adenylyl cyclase (tmAC). Pharmacological deactivation of sAC and tmAC decreased the CB cAMP content in normocapnia and IH with no differences between these two conditions. Changes from normocapnia to IH did not effect the degree of PKA activation and the carotid sinus nerve discharge frequency. sAC and tmAC are functional in CB but intracellular elevations in CO2/HCO3(-) in IH conditions on their own are insufficient to further activate these enzymes, suggesting that the hypercapnic response is dependent on secondary acidosis.

Details

Original languageEnglish
Pages (from-to)83-93
Number of pages11
JournalRespiratory physiology & neurobiology
Volume188
Issue number2
Publication statusPublished - 15 Aug 2013

Keywords

  • Action Potentials, Adenylyl Cyclases, Animals, Animals, Newborn, Bicarbonates, Carotid Body, Chemoreceptor Cells, Colforsin, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Dose-Response Relationship, Drug, Enzyme Inhibitors, Ganglia, Sensory, Gene Expression Regulation, Enzymologic, Hydrogen-Ion Concentration, Hypercapnia, Luminescent Proteins, Nucleotides, Cyclic, RNA, Messenger, Rats, Rats, Sprague-Dawley