Role of mitogen-activated protein kinases in endothelin ETB receptor up-regulation after organ culture of rat mesenteric artery

Cardiovascular risk factors regulate the expression of vascular endothelin receptors

“…ET B2 receptor activation following organ culture (Uddman et al, 2003). In vivo, U0126 diminishes the upregulated contractile responses and ET B2 receptor expression in rat middle cerebral arteries after occlusion ; this finding suggests that the MAPK-mediated upregulation of endothelin receptors may provide a new perspective on the pathophysiology and therapy of CVD.…”

“…These results suggest that PKC may play an important role in regulating ET B2 receptor expression. In parallel, the MAPK MEK/ERK pathway was involved in endothelin receptor upregulation both in vitro (Uddman et al, 2003) and in vivo (Beg et al, 2006). The PKC and the MEK/ERK pathways appear to interact, as demonstrated by a Western blot study (Ansar & Edvinsson, 2008).…”

Vascular endothelin ETB receptor-mediated contraction requires phosphorylation of ERK1/2 proteins

“…We have observed that the upregulation of endothelin ET B receptors can be mimicked by organ culture of arterial segments (Moller et al, 2002, Uddman et al, 2003and Adner et al, 1998a. It is well documented that in fresh mesenteric arteries of rat, there is no contractile response to sarafotoxin 6c, a selective endothelin ET B receptor agonist (Adner et al, 1998a).…”

“…This up-regulation of endothelin ET B receptors has been further documented in vascular disease in humans, including atherosclerotic arteries (Dagassan et al, 1996 andPernow et al, 2000), ischaemic heart disease (Wackenfors et al, 2004) and in cerebrovascular diseases (Hansen-Schwartz et al, 2003). The mechanisms responsible for the upregulation of endothelin ET B receptors involves gene transcription and include activation of protein kinase and mitogen-activated protein kinase (MAPK) pathways consist of ERK1/2 (Uddman et al, 2003). It has been observed that of MAPK and down stream transcriptional factors regulate the gene expression of G-protein-coupled receptors, such as endothelin ET B , 5-hydroxytryptamine (5-HT) 2A and bradykinin B 1 and B 2 receptors in response to extracellular stimuli (Cao et al, 2005, Zhang et al, 2004and Zhang et al, 2005.…”

“…The reagent SB386023 (a generous gift from Dr. A. A. Parsons, GSK, UK), a specific ERK1/2 inhibitor (Uddman et al, 2003), was dissolved into dimethylsulfoxide (DMSO), and SB386023 or DMSO were diluted to needed concentration with the DMEM solution. The protocol was approved by the Ethical Committee of Lund University (M 120-01).…”