Premium
ω‐hydroxylase modulates adenosine A 1 receptor‐induced vascular tone
Author(s) -
Kunduri Swati S,
Nayeem Mohammed A,
Ponnoth Dovenia S,
Tilley Stephen S,
Schnermann Jurgen,
Mustafa SJamal
Publication year - 2011
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.25.1_supplement.1115.15
Subject(s) - ccpa , protein kinase c , endocrinology , medicine , agonist , chemistry , adenosine , vasoconstriction , receptor , contraction (grammar) , adenosine receptor , pharmacology , kinase , biochemistry
We have shown earlier (Kunduri et al, FASEB J , 2010, 958.3) that A 1 AR‐induced vasoconstricton depends on CYP4A. These data showed that CYP4A inhibitor (HET0016, 10 −5 M) changed CCPA (A 1 AR selective agonist) induced contraction (5.7%± 2.3%, p<0.05) into relaxation (60.36± 13.7%, p<0.05) and ERK1/2 inhibitor (PD98059, 10 −5 M) blocked the 20‐HETE induced contraction in A 1 WT (9.4± 5.8%, p<0.05) vs. A 1 KO (2.9± 4.9%, p<0.05). We investigated in this study the signaling pathway due to A 1 AR stimulation causing vasoconstriction via CYP4A using A 1 WT and A 1 KO mouse aortas treated with HET0016 and CCPA.CCPA (10 −6 M) increased A 1 AR expression by 68%(p<0.05) in A 1 WT compared to A 1 KO (29.3%, p<0.05). Also, CCPA treatment enhanced the CYP4A expression by 66.7% (p <0.05) in A 1 WT compared to non‐treated (36.7%) and A 1 KO (11.9%, p<0.05). HET0016 significantly lowered the CYP4A expression by 16.8% in A 1 WT. CCPA up regulated PKC‐α by 70.2% (p< 0.05) in A 1 WT. However, PKC‐α level was unchanged in both treated and non‐treated A 1 KO aortas. CCPA significantly increased p‐ERK1/2expression by 49.7%, and the effects of CCPA on PKC‐α and p‐ERK 1/2 were blocked by HET0016 in both A 1 WT and A 1 KO (PKC‐α, p<0.05; p‐ERK1/2, p<0.05). These data show that A 1 AR induced vasoconstriction in mouse aorta is mediated through 20‐HETE→PKC‐α→p‐ERK1/2. (HL027339, HL094447, HL071802)