Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors
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Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors. / Nunes, Ana R; Holmes, Andrew P S; Sample, Vedangi; Kumar, Prem; Cann, Martin J; Monteiro, Emília C; Zhang, Jin; Gauda, Estelle B.
In: Respiratory physiology & neurobiology, Vol. 188, No. 2, 15.08.2013, p. 83-93.Research output: Contribution to journal › Article › peer-review
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T1 - Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors
AU - Nunes, Ana R
AU - Holmes, Andrew P S
AU - Sample, Vedangi
AU - Kumar, Prem
AU - Cann, Martin J
AU - Monteiro, Emília C
AU - Zhang, Jin
AU - Gauda, Estelle B
N1 - Copyright © 2013 Elsevier B.V. All rights reserved.
PY - 2013/8/15
Y1 - 2013/8/15
N2 - 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.
AB - 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.
KW - Action Potentials
KW - Adenylyl Cyclases
KW - Animals
KW - Animals, Newborn
KW - Bicarbonates
KW - Carotid Body
KW - Chemoreceptor Cells
KW - Colforsin
KW - Cyclic AMP
KW - Cyclic AMP-Dependent Protein Kinases
KW - Dose-Response Relationship, Drug
KW - Enzyme Inhibitors
KW - Ganglia, Sensory
KW - Gene Expression Regulation, Enzymologic
KW - Hydrogen-Ion Concentration
KW - Hypercapnia
KW - Luminescent Proteins
KW - Nucleotides, Cyclic
KW - RNA, Messenger
KW - Rats
KW - Rats, Sprague-Dawley
U2 - 10.1016/j.resp.2013.05.013
DO - 10.1016/j.resp.2013.05.013
M3 - Article
C2 - 23727159
VL - 188
SP - 83
EP - 93
JO - Respiratory physiology & neurobiology
JF - Respiratory physiology & neurobiology
SN - 1569-9048
IS - 2
ER -