uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Adenosine increases calcium sensitivity via receptor-independent activation of the p38/MK2 pathway in mesenteric arteries
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
Show others and affiliations
2008 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 193, no 1, 37-46 p.Article in journal (Refereed) Published
Abstract [en]

AIM: Adenosine (Ado) restores desensitized angiotensin II-induced contractions in the renal arterioles via an intracellular, receptor-independent mechanisms including the p38 mitogen-activated protein kinase (MAPK). In the present study we test the hypothesis that MAPK-activated protein kinase 2 (MK2) mediates the Ado effect downstream from p38 MAPK resulting in an increased phosphorylation of the regulatory unit of the myosin light chain (MLC(20)). METHODS AND RESULTS: Contraction experiments were performed in rings of mesenteric arteries under isometric conditions in C57BL6 and MK2 knock out mice (MK2-/-). Ado pretreatment (10(-5) mol L(-1)) strongly increased Ang II sensitivity, calcium sensitivity and the phosphorylation of MLC(20). Treatment with Ado (3 x 10(-6) or 10(-5) mol L(-1) in between successive Ang II applications) enhanced the desensitized Ang II responses (second to fifth application). Ca(2+) transients were not effected by Ado. Further, blockade of type 1 and type 2 Ado receptors during treatment did not influence the effect. Type 3 receptor activation by inosine instead of Ado had no effect. Conversely, inhibition of nitrobenzylthioinosine-sensitive Ado transporters prevented the effects of Ado. Inhibition of p38 MAPK as well as use of MK2-/- mice prevented contractile Ado effects on the mesenteric arteries and the phosphorylation of MLC(20). CONCLUSION: The study shows that Ado activates the p38 MAPK/MK2 pathway in vascular smooth muscle via an intracellular action, which results in an increased MLC(20) phosphorylation in concert with increased calcium sensitivity of the contractile apparatus. This mechanism can significantly contribute to the regulation of vascular tone, e.g. under post-ischaemic conditions.

Place, publisher, year, edition, pages
2008. Vol. 193, no 1, 37-46 p.
Keyword [en]
adenosine, angiotensin II, calcium sensitivity, MK2, myosin light chain, p38 MAPK
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104342DOI: 10.1111/j.1748-1716.2007.01800.xISI: 000254639300004PubMedID: 18005245OAI: oai:DiVA.org:uu-104342DiVA: diva2:219662
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Integrativ Fysiologi
In the same journal
Acta Physiologica
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 418 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf