Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)peer-review

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Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia. / Holmes, Andrew P; Nunes, Ana Rita; Cann, Martin J; Kumar, Prem.

Arterial Chemoreceptors in Physiology and Pathophysiology. ed. / Chris Peers; Prem Kumar; Christopher Wyatt; Estelle Gauda; Colin A. Nurse; Nanduri Prabhakar . Vol. 860 Springer, 2015. p. 279-289 (Advances in Experimental Medicine and Biology; Vol. 860).

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)peer-review

Harvard

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. in C Peers, P Kumar, C Wyatt, E Gauda, CA Nurse & N Prabhakar (eds), Arterial Chemoreceptors in Physiology and Pathophysiology. vol. 860, Advances in Experimental Medicine and Biology, vol. 860, Springer, pp. 279-289. https://doi.org/10.1007/978-3-319-18440-1_32

APA

Holmes, A. P., Nunes, A. R., Cann, M. J., & Kumar, P. (2015). Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia. In C. Peers, P. Kumar, C. Wyatt, E. Gauda, C. A. Nurse, & N. Prabhakar (Eds.), Arterial Chemoreceptors in Physiology and Pathophysiology (Vol. 860, pp. 279-289). (Advances in Experimental Medicine and Biology; Vol. 860). Springer. https://doi.org/10.1007/978-3-319-18440-1_32

Vancouver

Holmes AP, Nunes AR, Cann MJ, Kumar P. Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia. In Peers C, Kumar P, Wyatt C, Gauda E, Nurse CA, Prabhakar N, editors, Arterial Chemoreceptors in Physiology and Pathophysiology. Vol. 860. Springer. 2015. p. 279-289. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-3-319-18440-1_32

Author

Holmes, Andrew P ; Nunes, Ana Rita ; Cann, Martin J ; Kumar, Prem. / Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia. Arterial Chemoreceptors in Physiology and Pathophysiology. editor / Chris Peers ; Prem Kumar ; Christopher Wyatt ; Estelle Gauda ; Colin A. Nurse ; Nanduri Prabhakar . Vol. 860 Springer, 2015. pp. 279-289 (Advances in Experimental Medicine and Biology).

Bibtex

@inbook{913a8d1a0c0748e8b3e93842679ebcfb,
title = "Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia",
abstract = "Carotid body (CB) stimulation by hypercapnia causes a reflex increase in ventilation and, along with the central chemoreceptors, this prevents a potentially lethal systemic acidosis. Control over the CB chemoafferent output during normocapnia and hypercapnia most likely involves multiple neurotransmitters and neuromodulators including ATP, acetylcholine, dopamine, serotonin and adenosine, but the precise role of each is yet to be fully established. In the present study, recordings of chemoafferent discharge frequency were made from the isolated in vitro CB in order to determine the contribution of adenosine, derived specifically from extracellular catabolism of ATP, in mediating basal chemoafferent activity and responses to hypercapnia. Pharmacological inhibition of ecto-5'-nucleotidase (CD73), a key enzyme required for extracellular generation of adenosine from ATP, using α,β-methylene ADP, virtually abolished the basal normocapnic single fibre discharge frequency (superfusate PO(2) ~ 300 mmHg, PCO(2) ~ 40 mmHg) and diminished the chemoafferent response to hypercapnia (PCO(2) ~ 80 mmHg). These effects were mimicked by the blockade of adenosine receptors with 8-(p-sulfophenyl) theophylline. The excitatory impact of adenosinergic signalling on CB hypercapnic sensitivity is most likely to be conferred through changes in cAMP. Here, inhibition of transmembrane, but not soluble adenylate cyclases, reduced normocapnic single fibre activity and inhibited the elevation evoked by hypercapnia by approximately 50 %. These data therefore identify a functional role for CD73 derived adenosine and transmembrane adenylate cyclases, in modulating the basal chemoafferent discharge frequency and in priming the CB to hypercapnic stimulation.",
keywords = "carotid body, adenosine, hypercapnia, Ecto-5′-nucleotidase, cAMP",
author = "Holmes, {Andrew P} and Nunes, {Ana Rita} and Cann, {Martin J} and Prem Kumar",
year = "2015",
doi = "10.1007/978-3-319-18440-1_32",
language = "English",
isbn = "978-3319184395",
volume = "860",
series = "Advances in Experimental Medicine and Biology",
publisher = "Springer",
pages = "279--289",
editor = "Chris Peers and Prem Kumar and Christopher Wyatt and Estelle Gauda and Nurse, {Colin A.} and {Prabhakar }, Nanduri",
booktitle = "Arterial Chemoreceptors in Physiology and Pathophysiology",

}

RIS

TY - CHAP

T1 - Ecto-5'-nucleotidase, adenosine and transmembrane adenylyl cyclase signalling regulate basal carotid body chemoafferent outflow and establish the sensitivity to hypercapnia

AU - Holmes, Andrew P

AU - Nunes, Ana Rita

AU - Cann, Martin J

AU - Kumar, Prem

PY - 2015

Y1 - 2015

N2 - Carotid body (CB) stimulation by hypercapnia causes a reflex increase in ventilation and, along with the central chemoreceptors, this prevents a potentially lethal systemic acidosis. Control over the CB chemoafferent output during normocapnia and hypercapnia most likely involves multiple neurotransmitters and neuromodulators including ATP, acetylcholine, dopamine, serotonin and adenosine, but the precise role of each is yet to be fully established. In the present study, recordings of chemoafferent discharge frequency were made from the isolated in vitro CB in order to determine the contribution of adenosine, derived specifically from extracellular catabolism of ATP, in mediating basal chemoafferent activity and responses to hypercapnia. Pharmacological inhibition of ecto-5'-nucleotidase (CD73), a key enzyme required for extracellular generation of adenosine from ATP, using α,β-methylene ADP, virtually abolished the basal normocapnic single fibre discharge frequency (superfusate PO(2) ~ 300 mmHg, PCO(2) ~ 40 mmHg) and diminished the chemoafferent response to hypercapnia (PCO(2) ~ 80 mmHg). These effects were mimicked by the blockade of adenosine receptors with 8-(p-sulfophenyl) theophylline. The excitatory impact of adenosinergic signalling on CB hypercapnic sensitivity is most likely to be conferred through changes in cAMP. Here, inhibition of transmembrane, but not soluble adenylate cyclases, reduced normocapnic single fibre activity and inhibited the elevation evoked by hypercapnia by approximately 50 %. These data therefore identify a functional role for CD73 derived adenosine and transmembrane adenylate cyclases, in modulating the basal chemoafferent discharge frequency and in priming the CB to hypercapnic stimulation.

AB - Carotid body (CB) stimulation by hypercapnia causes a reflex increase in ventilation and, along with the central chemoreceptors, this prevents a potentially lethal systemic acidosis. Control over the CB chemoafferent output during normocapnia and hypercapnia most likely involves multiple neurotransmitters and neuromodulators including ATP, acetylcholine, dopamine, serotonin and adenosine, but the precise role of each is yet to be fully established. In the present study, recordings of chemoafferent discharge frequency were made from the isolated in vitro CB in order to determine the contribution of adenosine, derived specifically from extracellular catabolism of ATP, in mediating basal chemoafferent activity and responses to hypercapnia. Pharmacological inhibition of ecto-5'-nucleotidase (CD73), a key enzyme required for extracellular generation of adenosine from ATP, using α,β-methylene ADP, virtually abolished the basal normocapnic single fibre discharge frequency (superfusate PO(2) ~ 300 mmHg, PCO(2) ~ 40 mmHg) and diminished the chemoafferent response to hypercapnia (PCO(2) ~ 80 mmHg). These effects were mimicked by the blockade of adenosine receptors with 8-(p-sulfophenyl) theophylline. The excitatory impact of adenosinergic signalling on CB hypercapnic sensitivity is most likely to be conferred through changes in cAMP. Here, inhibition of transmembrane, but not soluble adenylate cyclases, reduced normocapnic single fibre activity and inhibited the elevation evoked by hypercapnia by approximately 50 %. These data therefore identify a functional role for CD73 derived adenosine and transmembrane adenylate cyclases, in modulating the basal chemoafferent discharge frequency and in priming the CB to hypercapnic stimulation.

KW - carotid body

KW - adenosine

KW - hypercapnia

KW - Ecto-5′-nucleotidase

KW - cAMP

U2 - 10.1007/978-3-319-18440-1_32

DO - 10.1007/978-3-319-18440-1_32

M3 - Chapter (peer-reviewed)

C2 - 26303492

SN - 978-3319184395

VL - 860

T3 - Advances in Experimental Medicine and Biology

SP - 279

EP - 289

BT - Arterial Chemoreceptors in Physiology and Pathophysiology

A2 - Peers, Chris

A2 - Kumar, Prem

A2 - Wyatt, Christopher

A2 - Gauda, Estelle

A2 - Nurse, Colin A.

A2 - Prabhakar , Nanduri

PB - Springer

ER -