Linkage between α1 Adrenergic Receptor and the Jak/STAT Signaling Pathway in Vascular Smooth Muscle Cells

Sasaguri, Toshiyuki; Teruya, Hiroshi; Ishida, Akio; Abumiya, Takeo; Ogata, Jun

doi:10.1006/bbrc.1999.2066

Cited by 33 publications

(26 citation statements)

References 36 publications

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“…The data presented in this study are also counterindicative of a vasoconstrictive role for ␣ 1B ARs. Our findings support an emerging hypothesis, which predicts that ␣ 1B ARs do not play a major role in contractile regulation in vascular smooth muscle (9) but rather are predominately coupled to various metabolic and cellular processes at vascular sites where the receptor is expressed (6,(37)(38)(39). This realization has important implications in the pharmacotherapeutic approach to the manipulation of blood pressure.…”

Section: Fig 4 Mean Femoral Artery Pressure (Basal Femoral Map)supporting

confidence: 82%

“…Regarding the ␣ 1B AR, however, the bulk of the literature suggests that this subtype does not play a significant role in the direct regulation of the peripheral vascular tone (5,9). Rather, the predominant role of ␣ 1B ARs expressed in the vasculature has been proposed to include the regulation of growth and metabolic activity (6,(37)(38)(39). Contrary to these studies, however, the ␣ 1B AR knockout mouse showed a decreased pressor response to phenylephrine infusion (8), which indicates the participation of the receptor in the regulation of peripheral vasoconstriction.…”

Section: Resultsmentioning

confidence: 99%

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Hypotension, Autonomic Failure, and Cardiac Hypertrophy in Transgenic Mice Overexpressing the α1B-Adrenergic Receptor

Zuscik

Chalothorn

Hellard

et al. 2001

Journal of Biological Chemistry

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␣ 1 -Adrenergic receptors (␣ 1A , ␣ 1B , and ␣ 1D ) are regulators of systemic arterial blood pressure and blood flow. Whereas vasoconstrictory action of the ␣ 1A and ␣ 1D subtypes is thought to be mainly responsible for this activity, the role of the ␣ 1B -adrenergic receptor (␣ 1B AR) in this process is controversial. We have generated transgenic mice that overexpress either wild type or constitutively active ␣ 1B ARs. Transgenic expression was under the control of the isogenic promoter, thus assuring appropriate developmental and tissue-specific expression. Cardiovascular phenotypes displayed by transgenic mice included myocardial hypertrophy and hypotension. Indicative of cardiac hypertrophy, transgenic mice displayed an increased heart to body weight ratio, which was confirmed by the echocardiographic finding of an increased thickness of the interventricular septum and posterior wall. Functional deficits included an increased isovolumetric relaxation time, a decreased heart rate, and cardiac output. Transgenic mice were hypotensive and exhibited a decreased pressor response. Vasoconstrictory regulation by ␣ 1B AR was absent as shown by the lack of phenylephrine-induced contractile differences between ex vivo mesenteric artery preparations. Plasma epinephrine, norepinephrine, and cortisol levels were also reduced in transgenic mice, suggesting a loss of sympathetic nerve activity. Reduced catecholamine levels together with basal hypotension, bradycardia, reproductive problems, and weight loss suggest autonomic failure, a phenotype that is consistent with the multiple system atrophy-like neurodegeneration that has been reported previously in these mice. These results also suggest that this receptor subtype is not involved in the classic vasoconstrictory action of ␣ 1 ARs that is important in systemic regulation of blood pressure.The adrenergic receptor family, which includes 3 ␣ 1 , 3 ␣ 2 , and 3 ␤-receptor subtypes, is a group of heptahelical G proteincoupled receptors that mediate the effects of the sympathetic nervous system. Extensive effort has been spent in classifying the three known ␣ 1 -adrenergic receptor (␣ 1 AR) 1 subtypes (␣ 1A , ␣ 1B , and ␣ 1D ) via molecular cloning techniques (1-4) and pharmacological analyses (5). The most well characterized cardiovascular regulatory actions associated with ␣ 1 AR activation include the contraction, growth and proliferation of vascular smooth muscle cells (6 -9), increased cardiac contractility (10), and regulation of the hypertrophic program in the myocardium (11,12). In other ␣ 1 AR-expressing tissues such as liver and kidney, the function of these receptors is to regulate metabolic processes (13) and sodium and water reabsorption (14), respectively. These responses are transduced primarily via receptor coupling to the G q /phospholipase C pathway (5), which leads to the subsequent activation of downstream signaling molecules including protein kinase C and inositol 1,4,5-trisphosphate.The progress toward elucidating the distinct regulatory role of each ␣ 1...

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Section: Fig 4 Mean Femoral Artery Pressure (Basal Femoral Map)supporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Hypotension, Autonomic Failure, and Cardiac Hypertrophy in Transgenic Mice Overexpressing the α1B-Adrenergic Receptor

Zuscik

Chalothorn

Hellard

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

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“…␣-Melanocyte-stimulating hormone, which enhances cellular proliferation, has been found to activate JAK2 and STAT1 in B-lymphocytes via stimulation of the melanocortin 5 receptor (13). Likewise, activation of ␣ 1 -adrenoceptors and protease-activated receptor 1 has been shown to induce tyrosine phosphorylation of JAK2, Tyk2, and STAT1 in vascular smooth muscle cells (14).…”

mentioning

confidence: 99%

Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism

Cheung²,

Wong

2003

Journal of Biological Chemistry

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“…Intracellular crosstalk Sasaguri et al were the first to report that α 1B -AR stimulation caused phosphorylation of tyrosine residues in JAK2 and STAT1 [47] . In particular, they showed that in vascular smooth muscle cells, phenylephrine-induced protein synthesis was dependent on STAT1 activation and could be inhibited by AG490, an inhibitor of JAK2.…”

Section: Crosstalk Between Ar Signaling and The Stat3 Pathwaymentioning

confidence: 99%

Crosstalk between signaling pathways of adrenoreceptors and signal transducers and activators of transcription 3 (STAT3) in heart

Gong

Zhang

et al. 2007

Acta Pharmacologica Sinica

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Recently, there have been important advancements in our understanding of the signaling mechanisms of adrenoreceptors (AR) and signal transducers and activators of transcription 3 (STAT3). While their crucial roles in the pathological processes of the heart are well established, accumulating evidence suggests there is a complex pattern of crosstalk between these 2 signaling pathways. Moreover, the potential for crosstalk occurs at multiple levels in each signaling cascade and involves receptor transactivation, G proteins, small GTPases, cyclic adenosine 3', 5'-monophosphate/protein kinase A, protein kinase C, scaffold/adaptor proteins, protein tyrosine kinases, and mitogen-activated protein kinases. In addition, posttranslational modification (eg acetylation) of STAT3 may provide a link between STAT3 and AR signaling. In particular, crosstalk between these 2 systems in the heart would appear to be dependent upon the species/tissue studied, developmental stage, and eliciting stimulus. This at least partly accounts for the epigenetic effects on biological function that is mediated by the 2 signaling pathways. Elucidation of these mechanisms will provide new targets in the development of novel clinical strategies for heart disorders.

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Linkage between α1 Adrenergic Receptor and the Jak/STAT Signaling Pathway in Vascular Smooth Muscle Cells

Cited by 33 publications

References 36 publications

Hypotension, Autonomic Failure, and Cardiac Hypertrophy in Transgenic Mice Overexpressing the α1B-Adrenergic Receptor

Hypotension, Autonomic Failure, and Cardiac Hypertrophy in Transgenic Mice Overexpressing the α1B-Adrenergic Receptor

Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism

Crosstalk between signaling pathways of adrenoreceptors and signal transducers and activators of transcription 3 (STAT3) in heart

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