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Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase‐null mice through cyp2j‐epoxygenases and PPARγ
Author(s) -
Nayeem Mohammed A,
Pradhan Isha,
Mustafa S Jamal,
Morisseau Christophe,
Falck John R,
Zeldin Darryl C
Publication year - 2013
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.27.1_supplement.1090.2
Subject(s) - epoxide hydrolase 2 , cgs 21680 , adenosine , agonist , chemistry , adenosine a2a receptor , antagonist , medicine , endocrinology , adenosine receptor , receptor , biochemistry , enzyme
The interaction between adenosine and sEH in vascular response is not known. Therefore, we hypothesized that lack of sEH enhances adenosine‐induced relaxation through A 2A AR via cyp2j‐epoxygenases and PPARγ. sEH −/− showed an increase in A 2A AR (31%), cyp2j (65%) & PPARγ (36%), and decrease in A 1 AR (30%) & PPARα (27%) vs. sEH +/+ . NECA (adenosine analog), CGS 21680 (A 2A AR‐agonist) & GW 7647 (PPARα‐agonist)‐induced responses were tested with L‐NAME (NO‐inhibitor), ZM‐241385, SCH‐58261 (A 2A AR‐antagonists), 14,15‐EEZE (EETs‐antagonist), AUDA, t‐ AUCB (sEH‐inhibitors) & T0070907 (PPARγ‐antagonist). NECA‐induced relaxation was higher in sEH −/− (+12.94 ± 3.2%) vs. sEH +/+ (−5.35 ± 5.2%), that was blocked by ZM‐241385 (−22.42 ± 1.9%) & SCH‐58261(−30.04 ± 4.2%). CGS‐21680‐induced relaxation was higher in sEH −/− (+37.4 ± 5.4%) vs. sEH +/+ (+2.14 ± 2.8%), that was not blocked by L‐NAME (p>;0.05), whereas 14,15‐EEZE did (p<0.05). Also, AUDA & t‐AUCB did not change CGS‐21680‐induced response in sEH −/− (p>;0.05), but reversed in sEH +/+ (AUDA: +45.33±4.1%, t ‐AUCB: +63.37±7.2). GW 7647 did not relax vs. CGS 21680 in sEH −/− (p<0.05), and T0070907 blocked CGS 21680 induced relaxation in sEH −/− (+9.40 ± 3.1). These data suggest that A 2A AR‐induced relaxation in sEH −/− may depend on the up‐regulation of cyp2j , PPARγ and down‐regulation of A 1 AR, PPARα. Supported (BGF‐WVU, STF‐WVU, HL027339 , HL094447 , GM31278 & z01 ES025034 ).