|Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ.|
|PMID: 23152114 Owner: NLM Status: MEDLINE|
|The interaction between adenosine and soluble epoxide hydrolase (sEH) in vascular response is not known. Therefore, we hypothesized that lack of sEH in mice enhances adenosine-induced relaxation through A(2A) adenosine receptors (AR) via CYP-epoxygenases and peroxisome proliferator-activated receptor γ (PPARγ). sEH(-/-) showed an increase in A(2A) AR, CYP2J, and PPARγ by 31%, 65%, and 36%, respectively, and a decrease in A(1)AR and PPARα (30% and 27%, respectively) vs. sEH(+/+). 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine receptor agonist), CGS 21680 (A(2A) AR-agonist), and GW 7647 (PPARα-agonist)-induced responses were tested with nitro-l-arginine methyl ester (l-NAME) (NO-inhibitor; 10(-4) M), ZM-241385, SCH-58261 (A(2A) AR-antagonists; 10(-6) M), 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an epoxyeicosatrienoic acid-antagonist; 10(-5) M), 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA; 10 μM) or trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB, sEH-inhibitors; 10(-5) M), and T0070907 (PPARγ-antagonist; 10(-7) M). In sEH(-/-) mice, ACh response was not different from sEH(+/+) (P > 0.05), and l-NAME blocked ACh-responses in both sEH(-/-) and sEH(+/+) mice (P < 0.05). NECA (10(-6) M)-induced relaxation was higher in sEH(-/-) (+12.94 ± 3.2%) vs. sEH(+/+) mice (-5.35 ± 5.2%); however, it was blocked by ZM-241385 (-22.42 ± 1.9%) and SCH-58261(-30.04 ± 4.2%). CGS-21680 (10(-6) M)-induced relaxation was higher in sEH(-/-) (+37.4 ± 5.4%) vs. sEH(+/+) (+2.14 ± 2.8%). l-NAME (sEH(-/-), +30.28 ± 4.8%, P > 0.05) did not block CGS-21680-induced response, whereas 14,15-EEZE (-7.1 ± 3.7%, P < 0.05) did. Also, AUDA and t-AUCB did not change CGS-21680-induced response in sEH(-/-) (P > 0.05), but reversed in sEH(+/+) (from +2.14 ± 2.8% to +45.33 ± 4.1%, and +63.37 ± 7.2, respectively). PPARα-agonist did not relax as CGS 21680 (-2.48 ± 1.1 vs. +37.4 ± 5.4%) in sEH(-/-), and PPARγ-antagonist blocked (from +37.4 ± 5.4% to +9.40 ± 3.1) CGS 21680-induced relaxation in sEH(-/-). Our data suggest that adenosine-induced relaxation in sEH(-/-) may depend on the upregulation of A(2A) AR, CYP2J, and PPARγ, and the downregulation of A(1) AR and PPARα.|
|Mohammed A Nayeem; Isha Pradhan; S Jamal Mustafa; Christophe Morisseau; John R Falck; Darryl C Zeldin|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-14|
|Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 304 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2013 Jan|
|Created Date: 2013-01-02 Completed Date: 2013-03-07 Revised Date: 2014-01-09|
Medline Journal Info:
|Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States|
|Languages: eng Pagination: R23-32 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
analogs & derivatives,
Adamantane / analogs & derivatives, pharmacology
Adenosine / analogs & derivatives, pharmacology
Adenosine A2 Receptor Agonists / pharmacology
Adenosine A2 Receptor Antagonists / pharmacology
Adenosine-5'-(N-ethylcarboxamide) / pharmacology
Benzamides / pharmacology
Benzoates / pharmacology
Butyrates / pharmacology
Enzyme Inhibitors / pharmacology
Epoxide Hydrolases / genetics, physiology*
Lauric Acids / pharmacology
NG-Nitroarginine Methyl Ester / pharmacology
Oxygenases / physiology*
PPAR gamma / physiology*
Phenethylamines / pharmacology
Phenylurea Compounds / pharmacology
Pyridines / pharmacology
Pyrimidines / pharmacology
Receptor, Adenosine A2A / physiology*
Triazines / pharmacology
Triazoles / pharmacology
Urea / analogs & derivatives, pharmacology
Vasodilation / drug effects, genetics, physiology
Vasodilator Agents / pharmacology
|GM-31278/GM/NIGMS NIH HHS; HL-027339/HL/NHLBI NIH HHS; HL-094447/HL/NHLBI NIH HHS; P01 DK038226/DK/NIDDK NIH HHS; R01 HL027339/HL/NHLBI NIH HHS; R01 HL094447/HL/NHLBI NIH HHS; Z01 ES025034/ES/NIEHS NIH HHS|
|0/12-(3-adamantan-1-ylureido)dodecanoic acid; 0/14,15-eicosa-5-enoic acid; 0/4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; 0/5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; 0/Adenosine A2 Receptor Agonists; 0/Adenosine A2 Receptor Antagonists; 0/Benzamides; 0/Benzoates; 0/Butyrates; 0/Enzyme Inhibitors; 0/GW 7647; 0/Lauric Acids; 0/PPAR gamma; 0/Phenethylamines; 0/Phenylurea Compounds; 0/Pyridines; 0/Pyrimidines; 0/Receptor, Adenosine A2A; 0/T 0070907; 0/Triazines; 0/Triazoles; 0/Vasodilator Agents; 0/ZM 241385; 120225-54-9/2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; 35920-39-9/Adenosine-5'-(N-ethylcarboxamide); 7324-41-6/8,11,14-Eicosatrienoic Acid; 8W8T17847W/Urea; EC 1.13.-/Oxygenases; EC 3.3.2.-/Epoxide Hydrolases; K72T3FS567/Adenosine; PJY633525U/Adamantane; V55S2QJN2X/NG-Nitroarginine Methyl Ester|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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