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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/H3448    most recent 00764.2007v1 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 Google Scholar Google Scholar Articles by Ansari, H. R. Articles by Mustafa, S. J. Search for Related Content PubMed PubMed Citation Articles by Ansari, H. R. Articles by Mustafa, S. J.

Involvement of COX-1 in A₃ adenosine receptor-mediated contraction through endothelium in mice aorta

¹Department of Physiology and Pharmacology, Center for Interdisciplinary Research in Cardiovascular Sciences, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia; ²Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Submitted 3 July 2007 ; accepted in final form 2 October 2007

We investigated whether A₃ adenosine receptor (A₃AR) is involved in endothelium-mediated contraction through cyclooxygenases (COXs) with the use of wild-type (WT) and A₃ knockout (A₃KO) mice aorta. A₃AR-selective agonist, Cl-IBMECA, produced a concentration-dependent contraction (EC₅₀: 2.9 ± 0.2 x 10^–9 M) in WT mouse aorta with intact endothelium (+E) and negligible effects in A₃KO +E aorta. At 10^–7 M, contractions produced by Cl-IBMECA were 29% in WT +E, while being insignificant in A₃KO +E aorta. Cl-IBMECA-induced responses were abolished in endothelium-denuded tissues (–E), in both WT and A₃KO aorta. A₃AR gene and protein expression were reduced by 74 and 72% (P < 0.05), respectively, in WT –E compared with WT +E aorta, while being undetected in A₃KO +E/–E aorta. Indomethacin (nonspecific COXs blocker, 10^–5 M), SC-560 (specific COX-1 blocker, 10^–8 M), SQ 29549 (thromboxane prostanoid receptor antagonist, 10^–6 M), and furegrelate (thromboxane synthase inhibitor, 10^–5 M) inhibited Cl-IBMECA-induced contraction significantly. Cl-IBMECA-induced thromboxane B₂ production was also attenuated significantly by indomethacin, SC-560, and furegrelate in WT +E aorta, while having negligible effects in A₃KO +E aorta. NS-398 (specific COX-2 blocker) produced negligible inhibition of Cl-IBMECA-induced contraction in both WT +E and A₃KO +E aorta. Cl-IBMECA-induced increase in COX-1 and thromboxane prostanoid receptor expression were significantly inhibited by MRS1523, a specific A₃AR antagonist in WT +E aorta. Expression of both A₃AR and COX-1 was located mostly on endothelium of WT and A₃KO +E aorta. These results demonstrate for the first time the involvement of COX-1 pathway in A₃AR-mediated contraction via endothelium.

endothelium; A₃ knockout; cyclooxygenases; thromboxane A₂ pathway; thromboxane prostanoid receptors; contraction