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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/H2574    most recent 00912.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Teng, B. Articles by Mustafa, S. J. Search for Related Content PubMed PubMed Citation Articles by Teng, B. Articles by Mustafa, S. J.

Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery

Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina

Submitted 2 September 2004 ; accepted in final form 5 January 2005

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 (EC₅₀ = 16.8 nM) of PGF₂ (10 µM)-preconstricted arterial rings. NECA-induced relaxation was completely blocked by 0.1 µM SCH-58261 (A_2A antagonist) at lower doses (1–40 nM) but not at higher doses (80–1,000 nM). MRS-1706 (1 µM, 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 N⁶-cyclopentyladenosine (A₁ agonist) and Cl-IB-MECA (A₃ agonist) did not. Furthermore, the effect of NECA was attenuated by the addition of SB-203580 (10 µM, p38 MAPK inhibitor) but not by PD-98059 (10 µM, MEK inhibitor). Interestingly, SB-203580 had no effect on CGS-21680-induced relaxation. Western blot analysis demonstrated that PGF₂ and adenosine agonists stimulated p38 MAPK at a concentration of 40 nM in PCA smooth muscle cells. MRS-1706 (1 µM) significantly reduced NECA-induced p38 MAPK phosphorylation. Addition of NECA and SB-203580 alone or in combination inhibited PGF₂-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.

adenosine receptors; vascular smooth muscle; p42/44; c-Jun NH₂-terminal kinase; prostaglandin F₂

This article has been cited by other articles:

				B. Teng, H. R. Ansari, P. J. Oldenburg, J. Schnermann, and S. J. Mustafa Isolation and characterization of coronary endothelial and smooth muscle cells from A1 adenosine receptor-knockout mice Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1713 - H1720. [Abstract] [Full Text] [PDF]