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Role of NADPH oxidase in A 3 adenosine receptor‐mediated contraction using knockout mouse aorta
Author(s) -
Ansari Habib R.,
Nadeem Ahmed,
Roush Kevin P.,
Tilley Stephen L.,
Mustafa S. Jamal
Publication year - 2009
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.23.1_supplement.937.5
Subject(s) - apocynin , nadph oxidase , chemistry , superoxide , kinase , phosphorylation , contraction (grammar) , knockout mouse , protein kinase a , adenosine , medicine , endocrinology , reactive oxygen species , biochemistry , receptor , biology , enzyme
Earlier we have reported that A 3 adenosine receptor (A 3 AR) mediated endothelial‐contraction is via COX‐1 pathway in mouse aorta ( Ansari et al Am J Physiol Heart Circ Physiol. 2007, 293:H3448‐55 ). In this study, we investigated signaling pathways coupled to A 3 AR activation using, Cl‐IBMECA in A 3 KO mouse aorta with apocynin (NADPH oxidase inhibitor) and PD98059 (p42/p44 MAP kinase inhibitor). We found that; a) treatment of aortic rings with Cl‐IBMECA resulted in NADPH oxidase subunits (gp91 & p47 phox) activation, p42/p44 MAP kinase phosphorylation and contraction, and b) preincubation of tissues with apocynin, PEG‐superoxide dismutase+PEG‐catalase and PD98059 inhibited A 3 AR‐induced aortic contraction significantly (p<.05). Cl‐IBMECA increased the ROS generation by 150±15% over control in WT which was inhibited by apocynin. In WT tissues, gp91 and p47 phox expressions were increased by 163±45% and 183±36%, respectively over control by Cl‐IBMECA which was blocked by apocynin. Cl‐IBMECA also increased p42/p44 MAP kinase phosphorylation by 116±42% over control and it was inhibited by PD98059 in WT. We conclude that Cl‐IBMECA leads to NADPH oxidase activation, ROS generation, p42/p44 MAP kinase phosphorylation which may play a role in A 3 AR‐mediated aortic contraction. Supported by HL‐027339, HL094447 and HL07180.