Adenosine Increases the cAMP Content of the Rat Carotid Body In Vitro

Monteiro, Emília C.; Vera-Cruz, Paulo; Monteiro, Teresa; Sousa, Maurício

doi:10.1007/978-1-4615-5891-0_45

Cited by 14 publications

(14 citation statements)

References 8 publications

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“…It is known that A 2 and D 2 receptors exert opposite actions on cAMP and that adenosine increases the cAMP content of rat CB (Monteiro et al. 1996).…”

Section: Resultsmentioning

confidence: 99%

An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

Conde

González

Batuca

et al. 2008

Journal of Neurochemistry

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We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A2B and dopamine D2 receptors present in chemoreceptor cells. Experiments were performed in vitro in CB from 3 months rats. The effect of A2B adenosine and D2 dopamine agonists and antagonists applied alone or in combination were studied on basal (20%O2) and hypoxia (10%O2)‐evoked release of CA and cAMP content of CB. We have found that adenosine A2 agonists and D2 antagonists dose‐dependently increased basal and evoked release CA from the CB while A2 antagonists and D2 agonists had an inhibitory action. The existence of A2B‐D2 receptor interaction was established because the inhibitory action of A2 antagonists was abolished by D2 antagonists, and the stimulatory action of A2 agonists was abolished by D2 agonists. Further, A2 agonists increased and D2 agonist decreased cAMP content in the CB; their co‐application eliminated the response. The present results provide direct pharmacological evidence that an antagonistic interaction between A2B adenosine and D2 dopamine receptors exist in rat CB and would explain the dopamine‐adenosine interactions on ventilation previously observed.

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“…It is known that A 2 and D 2 receptors exert opposite actions on cAMP and that adenosine increases the cAMP content of rat CB (Monteiro et al. 1996).…”

Section: Resultsmentioning

confidence: 99%

An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

Conde

González

Batuca

et al. 2008

Journal of Neurochemistry

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“…1986, 1987). It has also been described that adenosine increases cyclic AMP content in the rat CB (Monteiro et al . 1996), and that the increase in cyclic AMP produced by hypoxia in the rabbit is augmented by dipyridamole and blocked by A 2 antagonists (Chen et al .…”

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confidence: 89%

Hypoxia induces adenosine release from the rat carotid body

Conde

Monteiro

2004

Journal of Neurochemistry

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The effect of hypoxia on the release of adenosine was studied in vitro in the rat whole carotid body (CB) and compared with the effect of hypoxia (2%, 5% and 10% O 2 ) on adenosine concentrations in superior cervical ganglia (SCG) and carotid arteries. Moderate hypoxia (10% O 2 ) increased adenosine concentrations released from the CBs by 44%, but was not a strong enough stimulus to evoke adenosine release from SCG and arterial tissue. The extracellular pathways of adenosine production in rat CBs in normoxia and hypoxia were also investigated. S-(p-nitrobenzyl)-6-thioinosine (NBTI) and dipyridamole were used as pharmacological tools to inhibit adenosine equilibrative transporters (ENT) and a,b-methylene ADP (AOPCP) to inhibit ecto-5¢-nucleotidase. Approximately 40% of extracellular adenosine in the CB came from the extracellular catabolism of ATP, under both normoxic and hypoxic conditions. Low pO 2 triggers adenosine efflux through activation of NBTI-sensitive ENT. This effect was only apparent in hypoxia and when adenosine extracellular concentrations were reduced by the blockade of ecto-5¢-nucleotidase. We concluded that CB chemoreceptor sensitivity could be related to its low threshold for the release of adenosine in response to hypoxia here quantified for the first time. Keywords: adenosine, ATP, carotid body, ecto-5¢-nucleotidase, hypoxia, nucleoside transporter. The mammalian carotid bodies (CBs) are located in the bifurcation of common carotid arteries and are the main arterial pO 2 detectors, initiating compensatory reflex hyperventilation in response to a fall in blood oxygen levels. Although some controversies exist, there is a consensus that chemosensory activity in response to hypoxia is initiated in CB glomus cells (type I cells) which release excitatory neurotransmitters that activate synaptically apposed carotid sinus afferent nerve terminals (for a review see Gonzalez et al. 1994). The threshold tissue pO 2 for carotid sinus nerve discharge to increase oscillates between 55 and 65 mmHg, which corresponds to arterial blood pO 2 values of 70-75 mmHg (Obeso et al. 1997). In the present work we postulated that CB chemosensitivity to hypoxia could be associated with a low threshold for increasing the release of adenosine. To test this hypothesis, methodologies were developed that provide the first direct evidence concerning the effect of hypoxia on the release of adenosine from rat CBs. We use whole CBs due to the small dimensions of the organ which in the rat weighs approximately 40 lg and has a length of 600 lm (McDonald 1980). The CB's enormous blood flow is supplied by one artery originating from the carotid bifurcation area and the CB is also connected to the superior cervical ganglia by the ganglioglomerular nerves (Verna 1997). Carotid arteries and SCG were used as control preparations to assess the effect of hypoxia on the release of adenosine by non-chemosensitive structures present in the CB.The excitatory effects of adenosine on CB chemosensory activity were first described by McQu...

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“…After the removal of ZM-241385, adenosine was able to trigger a robust Ca 2ϩ signal in the same cell. A 2A receptors were reported to be coupled to the adenylate cyclase pathway (34) and A 2A receptor activation has been shown to increase the cAMP content in rabbit (5) and rat carotid body (29). In these 34 cells, the peak amplitude of the [Ca 2ϩ ] i rise elicited by adenosine alone was 153 Ϯ 76 nM but reduced to 45 Ϯ 35 nM in the presence of ZM-241385.…”

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confidence: 99%

Adenosine stimulates depolarization and rise in cytoplasmic [Ca²⁺] in type I cells of rat carotid bodies

Xu¹,

Xu²,

Tse³

et al. 2006

American Journal of Physiology-Cell Physiology

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During hypoxia, the level of adenosine in the carotid bodies increases as a result of ATP catabolism and adenosine efflux via adenosine transporters. Using Ca2+ imaging, we found that adenosine, acting via A2A receptors, triggered a rise in cytoplasmic [Ca2+] ([Ca2+]i) in type I (glomus) cells of rat carotid bodies. The adenosine response could be mimicked by forskolin (but not its inactive analog), and could be abolished by the PKA inhibitor H89. Simultaneous measurements of membrane potential (perforated patch recording) and [Ca2+]i showed that the adenosine-mediated [Ca2+]i rise was accompanied by depolarization. Ni2+, a voltage-gated Ca2+ channel (VGCC) blocker, abolished the adenosine-mediated [Ca2+]i rise. Although adenosine was reported to inhibit a 4-aminopyridine (4-AP)-sensitive K+ current, 4-AP failed to trigger any [Ca2+]i rise, or to attenuate the adenosine response. In contrast, anandamide, an inhibitor of the TWIK-related acid-sensitive K+-1 (TASK-1) channels, triggered depolarization and [Ca2+]i rise. The adenosine response was attenuated by anandamide but not by tetraethylammonium. Our results suggest that adenosine, acting via the adenylate cyclase and PKA pathways, inhibits the TASK-1 K+ channels. This leads to depolarization and activation of Ca2+ entry via VGCC. This excitatory action of adenosine on type I cells may contribute to the chemosensitivity of the carotid body during hypoxia.

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Adenosine Increases the cAMP Content of the Rat Carotid Body In Vitro

Cited by 14 publications

References 8 publications

An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

Hypoxia induces adenosine release from the rat carotid body

Adenosine stimulates depolarization and rise in cytoplasmic [Ca²⁺] in type I cells of rat carotid bodies

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Adenosine Increases the cAMP Content of the Rat Carotid Body In Vitro

Cited by 14 publications

References 8 publications

An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells

An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells

Hypoxia induces adenosine release from the rat carotid body

Adenosine stimulates depolarization and rise in cytoplasmic [Ca2+] in type I cells of rat carotid bodies

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An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

An antagonistic interaction between A_2B adenosine and D₂ dopamine receptors modulates the function of rat carotid body chemoreceptor cells

Adenosine stimulates depolarization and rise in cytoplasmic [Ca²⁺] in type I cells of rat carotid bodies