Evidence map›Paper›PMID 21270135›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2011

2'-AMP and 3'-AMP inhibit proliferation of preglomerular vascular smooth muscle cells and glomerular mesangial cells via A2B receptors.

Edwin K Jackson, Delbert G Gillespie, Raghvendra K Dubey

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. 2',3'-cGMP exists in vivo and comprises a 2',3'-cGMP-guanosine pathway.American journal of physiology. Regulatory, integrative and comparative physiology · 2019
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  11. In vivo cardiovascular pharmacology of 2',3'-cAMP, 2'-AMP, and 3'-AMP in the rat.The Journal of pharmacology and experimental therapeutics · 2013
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  15. The 2',3'-cAMP-adenosine pathway.American journal of physiology. Renal physiology · 2011
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 2 countries.

Edwin K JacksonDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 100 Technology Dr., Pittsburgh, PA 15219, USA. edj@pitt.edu
Delbert G Gillespie
Raghvendra K Dubey
University of Pittsburgh · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Role of Renal Dipeptidyl Peptidase IVR01HL069846 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JACKSON, EDWIN KERRY · 2003 to 2020
$6.6M
The Renal 2',3'-cAMP-Adenosine PathwayR01DK068575 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JACKSON, EDWIN KERRY · 2005 to 2016
$4.0M
NHLBI NIH HHS HL069846NHLBI NIH HHS R01 HL069846NIDDK NIH HHS DK068575NIDDK NIH HHS DK079307NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK068575
6 · The paper itself

Abstract

Studies show that kidneys produce 2',3'-cAMP, 2',3'-cAMP is exported and metabolized to 2'-AMP and 3'-AMP, 2'-AMP and 3'-AMP are metabolized to adenosine, 2',3'-cAMP inhibits proliferation of preglomerular vascular smooth muscle cells (PGVSMCs) and glomerular mesangial cells (GMCs), and A(2B) (not A(1), A(2A), or A(3)) adenosine receptors mediate part of the antiproliferative effects of 2',3'-cAMP. These findings suggest that extracellular 2',3'-cAMP attenuates proliferation of PGVSMCs and GMCs partly via conversion to corresponding AMPs, which are metabolized to adenosine that activates A(2B) receptors. This hypothesis predicts that extracellular 2'-AMP and 3'-AMP should exert A(2B) receptor-mediated antiproliferative effects. Therefore, we examined the antiproliferative effects (cell counts) of 2'-AMP and 3'-AMP. In PGVSMCs and GMCs, 2'-AMP and 3'-AMP exerted concentration-dependent antiproliferative effects. 3'-AMP was equipotent with and 2'-AMP was 3-fold less potent than 5'-AMP (prototypical adenosine precursor). In PGVSMCs, the effects of 2'-AMP and 3'-AMP were mimicked by adenosine, and 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl)xanthine (MRS-1754) (A(2B) receptor antagonist) equally blocked the antiproliferative effects of 2'-AMP, 3'-AMP, and adenosine but less effectively blocked the effects of 2',3'-cAMP. Similar results were obtained in GMCs except that MRS-1754 also incompletely blocked the effects of 3'-AMP. We conclude that in PGVSMCs, 2'-AMP and 3'-AMP are antiproliferative, the antiproliferative effects of 2'-AMP and 3'-AMP are mediated nearly entirely by adenosine/A(2B) receptors, and some of the antiproliferative effects of 2',3'-cAMP are independent of adenosine/A(2B) receptors. Similar conclusions apply to GMCs except that 3'-AMP also has actions independent of adenosine/A(2B) receptors. Because A(2B) receptors are renoprotective, 2'-AMP and 3'-AMP may provide renoprotection by generating adenosine that activates A(2B) receptors.

Indexed as

AcetamidesAdenosine MonophosphateAnimalsCell ProliferationCells, CulturedDose-Response Relationship, DrugMaleMesangial CellsMuscle, Smooth, VascularMyocytes, Smooth MusclePurinesRatsRats, Inbred WKYReceptor, Adenosine A2BAcetamidesAdenosine MonophosphateN-(4-cyanophenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy)acetamidePurinesReceptor, Adenosine A2B

Identifiers

PMID21270135
PMCPMC3083111
OpenAlexW2125872064

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.