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Adenosine enhances calcium sensitivity by intracellular mechanisms involving p38 MAPK/MK2 pathway in the mouse mesenteric artery
Author(s) -
Martinka Peter,
Fahling Michael,
Schmidt Sebastian,
Jankowski Vera,
Schubert Rudolf,
Gaestel Matthias,
Persson Pontus Börje,
Patzak Andreas
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1339-b
Subject(s) - adenosine , mesenteric arteries , intracellular , vasodilation , mapk/erk pathway , endocrinology , chemistry , medicine , vascular smooth muscle , microbiology and biotechnology , pharmacology , phosphorylation , biology , biochemistry , artery , smooth muscle
Adenosine (Ado) is produced excessively under ischemic or hypoxic conditions and induces profound vasodilation which is aimed to reduce the deleterious effects of ischemia. Here we show that exogenously applied Ado surprisingly increases Ca 2+ sensitivity and enhances phosphorylation of the myosin light chain (MLC 20 ) which almost completely re‐sensitizes repeated angiotensin II (Ang II) ‐induced contractions and increases dose‐dependent Ang II contractility of murine mesenteric arteries. This effect is intracellular and receptor‐independent, since blockade of all subtypes of Ado receptors showed no effect. Conversely, inhibition of NBTI‐sensitive adenosine transporters prevented the effects of Ado. Intracellular Ado action involves activation of the p38 MAPK/MK2 pathway, since p38 MAPK inhibition and use of MK2 −/− mice resulted in the prevention of Ado effects on the mesenteric arteries and phosphorylation of MLC 20 . Moreover, Ado increased intracellular levels of purinergic nucleotides and inosine as measured by MALDI‐mass spectrometry. In conclusion, Ado activates the p38 MAPK/MK2 pathway in vascular smooth muscle via intracellular action which results in an increased Ca 2+ sensitivity of the contractile apparatus. This mechanism can significantly contribute to the regulation of vascular tone, e.g. under ischemic conditions.