Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery. Am J Physiol Heart Circ Physiol 288:H2574-H2580

Dept. of Pharmacology and Toxicology, Brody School of Medicine, East Carolina Univ., Greenville, NC 27834, USA.
AJP Heart and Circulatory Physiology (Impact Factor: 3.84). 07/2005; 288(6):H2574-80. DOI: 10.1152/ajpheart.00912.2004
Source: PubMed


The purpose of this study was to explore the involvement of adenosine receptor(s) in porcine coronary artery (PCA) relaxation and to define the role of MAPK signaling pathways. Isometric tensions were recorded in denuded PCA rings. 5'-(N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine receptor agonist, induced a concentration-dependent relaxation (EC(50) = 16.8 nM) of PGF(2alpha) (10 microM)-preconstricted arterial rings. NECA-induced relaxation was completely blocked by 0.1 microM SCH-58261 (A(2A) antagonist) at lower doses (1-40 nM) but not at higher doses (80-1,000 nM). MRS-1706 (1 microM, A(2B) antagonist) was able to shift the NECA concentration-response curve to the right. CGS-21680 (selective A(2A) agonist) induced responses similarly to NECA, whereas N(6)-cyclopentyladenosine (A(1) agonist) and Cl-IB-MECA (A(3) agonist) did not. Furthermore, the effect of NECA was attenuated by the addition of SB-203580 (10 microM, p38 MAPK inhibitor) but not by PD-98059 (10 microM, MEK inhibitor). Interestingly, SB-203580 had no effect on CGS-21680-induced relaxation. Western blot analysis demonstrated that PGF(2alpha) and adenosine agonists stimulated p38 MAPK at a concentration of 40 nM in PCA smooth muscle cells. MRS-1706 (1 microM) significantly reduced NECA-induced p38 MAPK phosphorylation. Addition of NECA and SB-203580 alone or in combination inhibited PGF(2alpha)-induced p38 MAPK. Western blot data were further confirmed by p38 MAPK activity measurement using activating transcription factor-2 assay. Our results suggest that the adenosine receptor subtype involved in causing relaxation of porcine coronary smooth muscle is mainly A(2A) subtype, although A(2B) also may play a role, possibly through p38 MAPK pathway.

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Available from: Weixi Qin, Mar 12, 2015
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    • "Furthermore, the signaling pathways both up-and downstream of the p38 MAPK pathway are diverse, which may explain why p38 can be activated and create crosstalk among various stimuli (Eckle et al. 2007; Ono and Han 2000). For instance, it has been reported that p38 MAPK plays a significant role in angiotensin II-induced contraction (Meloche et al. 2000; Watts et al. 1998), while others have found that p38 MAPK is involved in adenosine-induced vasodilation (Teng et al. 2005). It is also possible that different p38 MAPK subtypes (p38 α , p38 β , and p38 γ ) are responsible for signaling via different pathways. "
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