We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dexmedetomidine-induced contraction involves c- Jun NH<sub>2</sub>-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta.
- Authors
Ok, Seong‐Ho; Byon, Hyo‐Jin; Jin, Hana; Kim, Hye Jung; Kim, Woochan; Nam, In‐Koo; Eun, So Young; Sohn, Ju‐Tae
- Abstract
Vasoconstriction induced by dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist, mainly involves c- Jun NH2-terminal kinase ( JNK) phosphorylation in the isolated endothelium-denuded aorta. We carried out an in vitro study to determine the main arachidonic acid metabolic pathway that is involved in dexmedetomidine-induced JNK activation. Cumulative dexmedetomidine concentration-contractile response curves were generated in the endothelium-denuded rat aorta in the presence or absence of the following inhibitors: the JNK inhibitor SP600125, the phospholipase A2 inhibitor quinacrine dihydrochloride, the non-specific lipoxygenase ( LOX) inhibitor nordihydroguaiaretic acid, the 5- LOX inhibitor AA-861, the dual 5- LOX and cyclooxygenase ( COX) inhibitor phenidone, the non-specific COX inhibitor indomethacin, the cytochrome p450 epoxygenase inhibitor fluconazole, the COX-1 inhibitor SC-560, and the COX-2 inhibitor NS-398. The effect of the alpha-2 adrenoceptor inhibitor rauwolscine and other inhibitors, such as quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, indomethacin and the protein kinase C inhibitor GF 109203X, on dexmedetomidine-induced JNK phosphorylation was investigated in rat aortic vascular smooth muscle cells with western blotting. The effect of dexmedetomidine on 5- LOX and COX-2 expression was investigated in vascular smooth muscle cells. SP600125, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, rauwolscine and chelerythrine attenuated dexmedetomidine-induced contraction. Indomethacin slightly attenuated dexmedetomidine-induced contraction. Fluconazole and SC-560 had no effect on dexmedetomidine-induced contraction, whereas NS-398 attenuated contraction. SP600125, rauwolscine, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone and GF 109203X attenuated dexmedetomidine-induced JNK phosphorylation. 5- LOX and COX-2 were upregulated by dexmedetomidine. Thus, dexmedetomidine-induced alpha-2 adrenoceptor-mediated contraction is mediated mainly by 5- LOX and partially by COX-2, which leads to JNK phosphorylation.
- Subjects
PHOSPHORYLATION; AORTA; LABORATORY rats; ARACHIDONIC acid; CYCLOOXYGENASES; VASCULAR smooth muscle
- Publication
Clinical & Experimental Pharmacology & Physiology, 2014, Vol 41, Issue 12, p1014
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12307