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.

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Nunes, Ana R ; Holmes, Andrew P S ; Sample, Vedangi ; Kumar, Prem ; Cann, Martin J ; Monteiro, Emília C ; Zhang, Jin ; Gauda, Estelle B. / Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors. In: Respiratory physiology & neurobiology. 2013 ; Vol. 188, No. 2. pp. 83-93.

Bibtex

@article{037d8b6dbba44e59b43a480232c3bade,
title = "Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors",
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.",
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",
author = "Nunes, {Ana R} and Holmes, {Andrew P S} and Vedangi Sample and Prem Kumar and Cann, {Martin J} and Monteiro, {Em{\'i}lia C} and Jin Zhang and Gauda, {Estelle B}",
note = "Copyright {\textcopyright} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = aug,
day = "15",
doi = "10.1016/j.resp.2013.05.013",
language = "English",
volume = "188",
pages = "83--93",
journal = "Respiratory physiology & neurobiology",
issn = "1569-9048",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

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 -