Cyclic AMP in Rat Ileum: Evidence for the Presence of an Extracellular Cyclic AMP-Adenosine Pathway

Giron, Maria Cecilia; Bin, Anna; Brun, Paola; Etteri, Sabrina; Bolego, Chiara; Florio, Chiara; Gaion, R.M.

doi:10.1053/j.gastro.2008.01.030

Cited by 49 publications

(57 citation statements)

References 30 publications

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“…Another possible source of extracellular ADO is the extracellular cAMP-ADO pathway, consisting of cAMP transporter, ecto-phosphodiesterase, and ecto-5Ј-nucleotidase (Gödecke, 2008). This pathway is observed in the skeletal muscle (Chiavegatti et al, 2008) and ileal muscle strip (Giron et al, 2008). Perfusion of the rat duodenum with cAMP, however, did not increase the rate of DBS, inconsistent with the presence of the cAMP-ADO pathway in rat duodenum (unpublished observations).…”

Section: Discussionmentioning

confidence: 89%

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Ham

Mizumori²,

Watanabe³

et al. 2010

J Pharmacol Exp Ther

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Luminal ATP increases duodenal bicarbonate secretion (DBS) via brush border P2Y receptors. Because ATP is sequentially dephosphorylated to adenosine (ADO) and the brush border highly expresses adenosine deaminase (ADA), we hypothesized that luminal [ADO] regulators and sensors, including P1 receptors, ADA, and nucleoside transporters (NTs) regulate DBS. We measured DBS with pH and CO 2 electrodes, perfusing ADO Ϯ adenosine receptor agonists or antagonists or the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR inh -172 on DBS. Furthermore, we examined the effect of inhibitors of ADA or NT on DBS. Perfusion of AMP or ADO (0.1 mM) uniformly increased DBS, whereas inosine had no effect. The A 1/2 receptor agonist 5Ј-(N-ethylcarboxamido)-adenosine (0.1 mM) increased DBS, whereas ADO-augmented DBS was inhibited by the potent A 2B receptor antagonist N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]-acetamide (MRS1754) (10 M). Other selective adenosine receptor agonists or antagonists had no effect. The A 2B receptor was immunolocalized to the brush border membrane of duodenal villi, whereas the A 2A receptor was immunolocalized primarily to the vascular endothelium. Furthermore, ADO-induced DBS was enhanced by 2Ј-deoxycoformycin (1 M) and formycin B (0.1 mM), but not by S-(4-nitrobenzyl)-6-thioinosine (0.1 mM), and it was abolished by CFTR inh -172 pretreatment (1 mg/kg i.p). Moreover, ATP (0.1 mM)-induced DBS was partially reduced by (1R,2S,4S,5S)-4-2-iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0] hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (MRS2500) or 8-[4-[4-(4-chlorophenzyl)piperazide-1-sulfonyl) phenyl]]-1-propylxanthine (PSB603) and abolished by both, suggesting that ATP is sequentially degraded to ADO. Luminal ADO stimulates DBS via A 2B receptors and CFTR. ATP release, ectophosphohydrolases, ADA, and concentrative NT may coordinately regulate luminal surface ADO concentration to modulate ADO-P1 receptor signaling in rat duodenum.

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Section: Discussionmentioning

confidence: 89%

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Ham

Mizumori²,

Watanabe³

et al. 2010

J Pharmacol Exp Ther

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“…In fact, it is important to emphasize that efflux of cAMP/ cGMP seems to be a widespread signaling mechanism (Hofer and Lefkimmiatis, 2007;Sager and Ravna, 2009) reported in vascular smooth muscle cells (Dubey et al, 1996), cardiac fibroblasts (Dubey et al, 2001), oviduct cells (Cometti et al, 2003), kidney (Jackson and Raghvendra, 2004;Dubey et al, 2010), adipose tissue (Strouch et al, 2005) gastrointestinal tract (Giron et al, 2008), human placenta explants (Biondi et al, 2010), astrocytes, and microglial cells (Verrier et al, 2011). Thus, the extracellular cAMP-adenosine pathway may represent a general autocrine and/or paracrine mechanism that indirectly modulates the signaling triggered by distinct receptors coupled to G s proteins, qualifying cyclic nucleotides as extracellular third messengers, and the extracellular cAMP-adenosine signaling pathway as a potential pharmacological target for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Duarte

Rodrigues

Godinho

2012

J Pharmacol Exp Ther

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␤ 2 -Adrenoceptor (␤ 2 -AR) agonists increase skeletal muscle contractile force via activation of G s protein/adenylyl cyclases (AC) and increased generation of cAMP. Herein, we evaluated the possible dual coupling of ␤ 2 -AR to G s and G i proteins and the influence of the ␤ 2 -AR/G s -G i /cAMP signaling cascade on skeletal muscle contraction. Assuming that the increment of intracellular cAMP is followed by cAMP efflux and extracellular generation of adenosine, the contribution of the extracellular cAMP-adenosine pathway on the ␤ 2 -AR inotropic response was also addressed. The effects of clenbuterol/fenoterol (␤ 2 -AR agonists), forskolin (AC activator), cAMP/8-bromo-cAMP, and adenosine were evaluated on isometric contractility of mouse diaphragm muscle induced by supramaximal direct electrical stimulation (0.1 Hz, 2 ms duration). Clenbuterol/fenoterol (10 -1000 M), 1 M forskolin, and 20 M rolipram induced transient positive inotropic effects that peaked 30 min after stimulation onset, declining to 10 to 20% of peak levels in 30 min.The late descending phase of the ␤ 2 -AR agonist inotropic effect was mimicked by either cAMP or adenosine and abolished by preincubation of diaphragm with pertussis toxin (PTX) (G i signaling inhibitor) or the organic anion transporter inhibitor probenecid, indicating a delayed coupling of ␤ 2 -AR to G i protein which depends on cAMP efflux. Remarkably, the PTX-sensitive ␤ 2 -AR inotropic effect was inhibited by the A 1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine and ecto-5Ј-phosphodiesterase inhibitor ␣,␤-methyleneadenosine 5Ј-diphosphate sodium salt, indicating that ␤ 2 -AR coupling to G i is indirect and dependent on A 1 receptor activation. The involvement of the extracellular cAMP-adenosine pathway in ␤ 2 -AR signaling would provide a negative feedback loop that may limit stimulatory G protein-coupled receptor positive inotropism and potential deleterious effects of excessive contractile response.

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“…GPC glycerophosphorylcholine, LPC lysophosphatidylcholine, pNPPC p-nitrophenyl phosphorylcholine, SPC sphingosylphosphorylcholine substrate [354][355][356][357]. There is ample evidence for the hydrolysis of extracellular cAMP by intact cells but the responsible enzyme has not been clearly identified [358,359]. Nucleoside monophosphates such as AMP or UMP are not hydrolyzed but exert competitive product inhibition of the NPP reaction [354,356,360,361].…”

Section: General Properties and Functional Rolementioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

872

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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Cyclic AMP in Rat Ileum: Evidence for the Presence of an Extracellular Cyclic AMP-Adenosine Pathway

Cited by 49 publications

References 30 publications

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle

Cellular function and molecular structure of ecto-nucleotidases

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Cyclic AMP in Rat Ileum: Evidence for the Presence of an Extracellular Cyclic AMP-Adenosine Pathway

Cited by 49 publications

References 30 publications

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β2-Adrenoceptors to Gsand GiProteins in Mouse Skeletal Muscle

Cellular function and molecular structure of ecto-nucleotidases

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Product

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About

Contribution of the Extracellular cAMP-Adenosine Pathway to Dual Coupling of β₂-Adrenoceptors to G_sand G_iProteins in Mouse Skeletal Muscle