Role of Omega-hydroxylase in adenosine-mediated aortic response through MAP kinase using A_(2A)-receptor knockout mice

摘要

On the other hand, 20-hydroxyeicosatrienoic acid (20-HETE), a Omega-hydroxylation product of A A catalyzed by Cyp4a, is a potent vasoconstrictor (36). Several studies have shown a link between vascular 20-HETE generation and responses in various vascular beds, including renal, cerebral, skeletal, and mesenteric (7, 8, 18). Increase in intracellular Ca~(2+) in smooth muscle causes an increase in 20-HETE (13), and, subsequent to this, 20-HETE inhibits Ca~(2+)-dependent K~+ channels, resulting in increase in vascular tone (14). Previously, we have found that, in A_(2A) knockout (KO) aorta, the use of A_1-selective antagonist blunted the contraction response, suggesting a role for A_1AR-mediated contraction (32). A_1AR is coupled to G_(i/o) proteins, and its activation results in a decrease in cyclic AMP through inhibition of adenylate cyclase (20). Studies have also shown that A_1AR activates p42/44 MAPK (ERK1/2) in vascular tissue and different cell lines (4, 16, 37). This activation may involve protein kinase A, protein kinase C (PKC), Src tyrosine kinase, or Ras activation (30, 38).