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

Luo, Gaoxing; Jamali, Roya; Cao, Yunxia; Edvinsson, Lars; Xu, Cang‐Bao

doi:10.1016/j.ejphar.2006.03.057

Cited by 22 publications

(18 citation statements)

References 32 publications

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“…The Raf-1/MEK/ERK signal transduction cascade has traditionally only been associated with growth-related processes such as activation of gene transcription [11] . However, recent studies have shown that this pathway can be involved in other, seemingly unrelated processes, such as vasoconstriction [6][7][8] . As contractile agonists have been shown to stimulate Raf-1 kinase in vascular smooth muscle cells grown in culture [18,32,33] , it is possible that a similar activation in blood vessels mediates vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

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Raf-1 Kinase Regulates Smooth Muscle Contraction in the Rat Mesenteric Arteries

et al. 2010

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Section: Discussionmentioning

confidence: 99%

“…There is convincing evidence to explain that the downstream effectors, MEK/ERK, regulate vascular contraction [6][7][8] . However, modulation of smooth muscle contraction by MEK/ERK has been shown to be directly regulated by PKC rather than its classical activator, Raf-1 [7,9,10] .…”

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confidence: 99%

Raf-1 Kinase Regulates Smooth Muscle Contraction in the Rat Mesenteric Arteries

et al. 2010

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“…It was previously shown that sensitivity to NA increased after a 7-day serum-free organ culture of rabbit mesenteric arteries [22]. Similarly, it was reported that sensitivity to an ET B agonist, sarafotoxin 6c increased after a 1-day serum-free organ culture of rat mesenteric arteries [7,11,18,19]. Several explanations are available to the increased sensitivity to agonists after serumfree organ culture; 1) up-regulation of receptor to each agonist, 2) activation of intercellular signaling pathways such as tyrosine kinase or protein kinase C (PKC), 3) increase in resting membrane potential by decreasing the expression and/or function of K + channels, or by increasing the expression and/or function of voltage-dependent Ca 2+ channels and transient receptor potential channel (TRPC), 4) production of reactive-oxygen species (ROS).…”

Section: Discussionmentioning

confidence: 98%

“…Several explanations are available to the increased sensitivity to agonists after serumfree organ culture; 1) up-regulation of receptor to each agonist, 2) activation of intercellular signaling pathways such as tyrosine kinase or protein kinase C (PKC), 3) increase in resting membrane potential by decreasing the expression and/or function of K + channels, or by increasing the expression and/or function of voltage-dependent Ca 2+ channels and transient receptor potential channel (TRPC), 4) production of reactive-oxygen species (ROS). In rat mesenteric arteries cultured for 1 day in the serum-free medium, the upregulation of alpha 1A adrenoreceptor [3] and ET B receptor [7,11,18,19] was reported. With regard to the activation of intercellular signal pathways, a non-receptor tyrosine kinase, src-dependent increase of NA-induced contraction was reported in rat mesenteric arteries cultured in the serumfree condition for 2-3 days [16].…”

Section: Discussionmentioning

confidence: 99%

Contractile Characteristics of Rat Mesenteric Artery after Organ Culture

Morita

Yamawaki

Okada

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. Organ culture of blood vessels is a useful technique to analyze long-term effects of drugs. Various growth factors are responsible for structural and functional changes during vascular remodeling. We investigated 1) basic contractile characteristics in organ-cultured rat mesenteric arteries (MA) in serum-free condition and 2) long-term effects of fetal bovine serum (FBS). Rat isolated MA with [E (+)] or without [E (-)] endothelium were divided into 1) freshly isolated (fresh), 2) cultured for 3 days without FBS (control) or 3) with 10% FBS (FBS). In E (+) control, maximal contraction by noradrenaline (NA), endothelin (ET)-1 and 5-hydroxytriptamine (5-HT) was similar to that in fresh. In E (-) control, maximal contraction by NA decreased whereas that by ET-1 and 5-HT didn't change from fresh. In E (+) FBS, maximal contraction by NA, ET-1, and 5-HT increased from control. In E (-) FBS, maximal contraction by NA and ET-1 decreased whereas that by 5-HT increased. In E (+) or E (-) control and FBS, sensitivity to NA and ET-1 increased from fresh. In E (+) and E (-) control, sensitivity to 5-HT decreased from fresh, and that in FBS further decreased from control. Three-day organ-cultured rat MA in serum-free condition preserved enough contraction to enable analysis for long-term effects of drug. In FBS, maximal contractions by NA and ET-1 increased in E (+) and decreased in E (-) from control, while those by 5-HT increased in both E (+) and E (-).KEY WORDS: blood vessel, cardiovascular pharmacology, contraction, growth factor, smooth muscle.J. Vet. Med. Sci. 72(12): 1621-1627, 2010 In order to sturdy the long-term effects of drugs, animal models have been used extensively. However, due to complicated in vivo kinetics and individual differences, analysis and interpretation of data is often difficult. In contrast, cell culture techniques make it possible to investigate direct effects of drugs and easily control experimental conditions. However, in the cell culture condition, tissue architectures and tissue specific functions are not completely preserved. Furthermore, it is difficult to examine the long-term effects of drugs using cultured vascular cells. Organ culture of blood vessels is thought to be a useful technique to analyze the long-term effects of drugs because it is possible to free from complicated factors existing in vivo and better preserve the differentiated cell functions [21,22].Due to easy handling and management, rats have been used widely in the fields of experimental medicine such as physiology and pharmacology. A rat genome has been clarified, and the most rat genes correspond to those of humans and mice [4]. Since inbred and mutant strains have been established in rats, experiments using rats are reproducible and reliable. However, there are only a few reports that investigated the basic contractile characteristics after longterm organ culture of rat mesenteric artery.Vascular remodeling occurs in cardiovascular disorders such as hypertension, atherosclerosis and diabetes. Various growth f...

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“…These results failed to demonstrate that there is alteration of contractile proteins in our system. Moreover, in previous investigations, organ culture of rat mesenteric arteries has been revealed to up-regulate vascular receptors like ET B receptors [27, 51]. The enhanced expression of the ET B receptors occurs through de novo transcription and is again not the result of an increase in general vascular reactivity [28].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Down-Regulation of Thromboxane A<sub>2</sub> Receptor Expression via Activation of MAPK ERK1/2, p38/NF-κB Pathways

Zhang¹,

Zhang

Edvinsson

et al. 2008

J Vasc Res

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Background: We have developed an in vitro model by organ culture of rat mesenteric arteries to imitate vascular smooth muscle cell (VSMC) receptor changes in cardiovascular disease. By using this model, alteration of VSMC thromboxane A₂ (TP) receptors was studied. Methods and Results:After organ culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions. Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-κB (NF-κB) was seen by Western blot within 1–3 h after organ culture. Inhibition of ERK1/2, p38 or NF-κB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D abolished decreased TP receptor-mediated contraction, while inhibition of translation, cyclooxygenase or nitric oxide synthase had no effect. TP receptor mRNA stability was unchanged during organ culture. Conclusions:The present study has demonstrated for the first time that organ culture of rat mesenteric arteries down-regulates VSMC TP receptor expression through activation of ERK1/2 and p38/NF-κB signal pathways.

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

Cited by 22 publications

References 32 publications

Raf-1 Kinase Regulates Smooth Muscle Contraction in the Rat Mesenteric Arteries

Raf-1 Kinase Regulates Smooth Muscle Contraction in the Rat Mesenteric Arteries

Contractile Characteristics of Rat Mesenteric Artery after Organ Culture

Transcriptional Down-Regulation of Thromboxane A<sub>2</sub> Receptor Expression via Activation of MAPK ERK1/2, p38/NF-κB Pathways

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