Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ

Mohammed A. Nayeem, Isha Pradhan, S. Jamal Mustafa, Christophe Morisseau, J R Falck, Darryl C. Zeldin

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 A2A adenosine receptors (AR) via CYP-epoxygenases and peroxisome proliferator-activated receptor γ (PPARγ). sEH-/- showed an increase in A2A AR, CYP2J, and PPARγ by 31%, 65%, and 36%, respectively, and a decrease in A1AR and PPARγ (30% and 27%, respectively) vs. sEH+/+. 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine receptor agonist), CGS 21680 (A2A 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 (A2A 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 PPARα-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 A2A AR, CYP2J, and PPARγ, and the downregulation of A1 AR and PPARα.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume304
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Adenosine A2A Receptors
Epoxide Hydrolases
Peroxisome Proliferator-Activated Receptors
Blood Vessels
Adenosine-5'-(N-ethylcarboxamide)
NG-Nitroarginine Methyl Ester
Adenosine
Adenosine A2 Receptor Agonists
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Agonists

Keywords

  • Adenosine A receptor
  • Adenosine A receptor
  • Contraction
  • CYP2J5-epoxgenase;ω-hydroxylase
  • Relaxation
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Medicine(all)

Cite this

Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ. / Nayeem, Mohammed A.; Pradhan, Isha; Mustafa, S. Jamal; Morisseau, Christophe; Falck, J R; Zeldin, Darryl C.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 304, No. 1, 01.01.2013.

Research output: Contribution to journalArticle

@article{51a13f3a8cae4e03a34a4e75126b458b,
title = "Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ",
abstract = "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 A2A adenosine receptors (AR) via CYP-epoxygenases and peroxisome proliferator-activated receptor γ (PPARγ). sEH-/- showed an increase in A2A AR, CYP2J, and PPARγ by 31{\%}, 65{\%}, and 36{\%}, respectively, and a decrease in A1AR and PPARγ (30{\%} and 27{\%}, respectively) vs. sEH+/+. 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine receptor agonist), CGS 21680 (A2A 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 (A2A 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 PPARα-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 A2A AR, CYP2J, and PPARγ, and the downregulation of A1 AR and PPARα.",
keywords = "Adenosine A receptor, Adenosine A receptor, Contraction, CYP2J5-epoxgenase;ω-hydroxylase, Relaxation, Soluble epoxide hydrolase",
author = "Nayeem, {Mohammed A.} and Isha Pradhan and Mustafa, {S. Jamal} and Christophe Morisseau and Falck, {J R} and Zeldin, {Darryl C.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1152/ajpregu.00213.2012",
language = "English (US)",
volume = "304",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ

AU - Nayeem, Mohammed A.

AU - Pradhan, Isha

AU - Mustafa, S. Jamal

AU - Morisseau, Christophe

AU - Falck, J R

AU - Zeldin, Darryl C.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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 A2A adenosine receptors (AR) via CYP-epoxygenases and peroxisome proliferator-activated receptor γ (PPARγ). sEH-/- showed an increase in A2A AR, CYP2J, and PPARγ by 31%, 65%, and 36%, respectively, and a decrease in A1AR and PPARγ (30% and 27%, respectively) vs. sEH+/+. 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine receptor agonist), CGS 21680 (A2A 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 (A2A 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 PPARα-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 A2A AR, CYP2J, and PPARγ, and the downregulation of A1 AR and PPARα.

AB - 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 A2A adenosine receptors (AR) via CYP-epoxygenases and peroxisome proliferator-activated receptor γ (PPARγ). sEH-/- showed an increase in A2A AR, CYP2J, and PPARγ by 31%, 65%, and 36%, respectively, and a decrease in A1AR and PPARγ (30% and 27%, respectively) vs. sEH+/+. 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine receptor agonist), CGS 21680 (A2A 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 (A2A 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 PPARα-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 A2A AR, CYP2J, and PPARγ, and the downregulation of A1 AR and PPARα.

KW - Adenosine A receptor

KW - Adenosine A receptor

KW - Contraction

KW - CYP2J5-epoxgenase;ω-hydroxylase

KW - Relaxation

KW - Soluble epoxide hydrolase

UR - http://www.scopus.com/inward/record.url?scp=84871879147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871879147&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00213.2012

DO - 10.1152/ajpregu.00213.2012

M3 - Article

VL - 304

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1

ER -