Structure and function of adenosine receptors and their genes

Fredholm, Bertil B.; Arslan, Giulia; Halldner, Linda; Kull, Björn; Schulte, Gunnar; Wasserman, Wyeth W.

doi:10.1007/s002100000313

Cited by 511 publications

(512 citation statements)

References 63 publications

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“…Table 1 compares averaged beat frequencies of sperm bathed (1-5 min) in HS medium alone, with Cl-dAdo, or with agonists selective for the 3 families (A1R, A2R, and A3R) of adenosine receptors that have been defined by pharmacological response and binding profiles (13). The resting beat frequency (in HS alone) was ϳ3-3.5 Hz, and increased ϳ2-fold in the presence of Cl-dAdo, consistent with Figs.…”

Section: Resultsmentioning

confidence: 99%

“…In some somatic cells, adenosine activates cell surface G-protein-coupled adenosine receptors that couple to various conventional transmembrane adenylyl cyclases (ADCY1-9) to control synthesis of cAMP (12,13). However, in sperm the predominant (perhaps the only) adenylyl cyclase is the atypical SACY (ADCY10) (8), which lacks transmembrane domains and is unaffected by G-proteins (14,15).…”

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confidence: 99%

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Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Burnett¹,

Blais²,

Unadkat

et al. 2010

Journal of Biological Chemistry

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Adenosine is a candidate modulator of sperm motility in the female reproductive tract that increases sperm flagellar beat frequency in vitro. Past work suggested that this acceleration may involve equilibrative (ENT) and concentrative (CNT) nucleoside transporters. Here we show that Slc29a1 (ENT-1) is the predominant nucleoside transporter expressed in the mouse testis. Unexpectedly, the beat of Slc29a1-null sperm still accelerates in response to 2-chloro-2-deoxyadenosine (Cl-dAdo). The only known roles of sperm are to reach the egg and deliver its genetic payload and to initiate early signaling events in the zygote. Although the list is short, the tasks are complex, and the sperm requires numerous specialized components to accomplish these goals. Our recent work has focused on how the sperm applies its specialized components to control swimming behavior. We have combined biophysical methods with a genetic approach, using sperm from null-mutant (knock-out) mice that carry targeted disruptions of the genes for several of the components of the signaling pathways that operate in the sperm flagellum. This approach has provided definitive evidence for required roles of the unique CatSper ion channel proteins (1-7), for the atypical sperm adenylyl cyclase SACY 2

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Burnett¹,

Blais²,

Unadkat

et al. 2010

Journal of Biological Chemistry

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“…Adenosine accumulates during hypoxia and ischemia and has a neuroprotective role (Goldberg et al 1988;Von Lubitz et al 1988;Cunha 2005) reducing the brains energy requirements during periods of metabolic stress. The actions of adenosine are well characterised, it acts via multiple cell surface G-protein coupled receptors: A 1 , A 2A , A 2B and A 3 (Fredholm et al 2000). The major effect of adenosine is to dampen down network excitation via A 1 receptor activation.…”

Section: Introductionmentioning

confidence: 99%

A population of immature cerebellar parallel fibre synapses are insensitive to adenosine but are inhibited by hypoxia

Atterbury

Wall

2011

Neuropharmacology

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Publisher statement: "NOTICE: this is the author's version of a work that was accepted for publication in Neuropharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropharmacology, VOL 61, ISSUE 4, 2011, DOI: 10.1016/j.neuropharm.2011 AbstractThe purine adenosine plays an important role in a number of physiological and pathological processes and is neuroprotective during hypoxia and ischemia. The major effect of adenosine is to suppress network activity via the activation of A 1 receptors. Here we report that in immature cerebellar slices, the activation of A 1 receptors has variable effects on parallel fibre synaptic transmission, ranging from zero depression to an almost complete abolition of transmission. Concentrationresponse curves suggest that the heterogeneity of inhibition stems from differences in A 1 receptor properties which could include coupling to downstream effectors. There is less variation in the effects of adenosine at parallel fibre synapses in slices from older rats and thus adenosine signalling appears developmentally regulated.In the cerebellum, hypoxia increases the concentration of extracellular adenosine leading to the activation of A 1 receptors (at adenosine-sensitive parallel fibre synapses) and the suppression of glutamate release. It would be predicted that the synapses that were insensitive to adenosine would be less depressed by hypoxia and thus maintain function during metabolic stress. However those synapses which were insensitive to adenosine were rapidly inhibited by hypoxia via a mechanism which was not reversed by blocking A 1 receptors. Thus another mechanism must be responsible for the hypoxia-mediated depression at these synapses. These different mechanisms of depression maybe important for cell survival and for maintenance of cerebellar function following oxygen starvation.3

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“…With an overall coronary vasodilation, A 2A AR predominantly and A 2B AR minimally contribute to dilating coronary vasculature [14][15][16], whereas A 1 AR and A 3 AR counteract the effects of A 2A /A 2B ARs resulting in a diminished coronary vasodilation [15,17,18]. At post-receptor levels, several effector pathways of adenosine-mediated coronary flow have been reported, such as activation of nitric oxide (NO) pathway [19,20], cyclic adenosine 5′-monophosphate (cAMP)-dependent pathway [21], activation of potassium channels [9,21], and the involvement of H 2 O 2 [19]. However, the downstream effectors linked to the activation of ARs in this process are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts

Zhou

Rajamani

Labazi

et al. 2015

Purinergic Signalling

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Adenosine increases coronary flow mainly through the activation of A 2A and A 2B adenosine receptors (ARs). However, the mechanisms for the regulation of coronary flow are not fully understood. We previously demonstrated that adenosine-induced increase in coronary flow is in part through NADPH oxidase (Nox) activation, which is independent of activation of either A 1 or A 3 ARs. In this study, we hypothesize that adenosine-mediated increase in coronary flow through Nox activation depends on A 2A but not A 2B ARs. Functional studies were conducted using isolated Langendorff-perfused mouse hearts. Hydrogen peroxide (H 2 O 2 ) production was measured in isolated coronary arteries from WT, A 2A AR k n o c k o u t ( K O ) , a n d A 2 B A R K O m i c e u s i n g dichlorofluorescein immunofluorescence. Adenosineinduced concentration-dependent increase in coronary flow was attenuated by the specific Nox2 inhibitor gp91 ds-tat or reactive oxygen species (ROS) scavenger EUK134 in both WT and A 2B but not A 2A AR KO isolated hearts. Similarly, the A 2A AR selective agonist CGS-21680-induced increase in coronary flow was significantly blunted by Nox2 inhibition in both WT and A 2B AR KO, while the A 2B AR selective agonist BAY 60-6583-induced increase in coronary flow was not affected by Nox2 inhibition in WT. In intact isolated coronary arteries, adenosine-induced (10 μM) increase in H 2 O 2 formation in both WT and A 2B AR KO mice was attenuated by Nox2 inhibition, whereas adenosine failed to increase H 2 O 2 production in A 2A AR KO mice. In conclusion, adenosine-induced increase in coronary flow is partially mediated by Nox2-derived H 2 O 2 , which critically depends upon the presence of A 2A AR.

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Structure and function of adenosine receptors and their genes

Cited by 511 publications

References 63 publications

Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

Testicular Expression of Adora3i2 in Adora3 Knockout Mice Reveals a Role of Mouse A3Ri2 and Human A3Ri3 Adenosine Receptors in Sperm*

A population of immature cerebellar parallel fibre synapses are insensitive to adenosine but are inhibited by hypoxia

Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts

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