Different Effects of Thrombin Receptor Activation on Endothelium and Smooth Muscle Cells of Human Coronary Bypass Vessels

Circulation ◽  
1997 ◽  
Vol 95 (7) ◽  
pp. 1870-1876 ◽  
Author(s):  
Zhihong Yang ◽  
Frank Ruschitzka ◽  
Ton J. Rabelink ◽  
Georg Noll ◽  
Friedgard Julmy ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Bypass ◽  
Muscle Cells ◽  
Receptor Activation ◽  
Thrombin Receptor

Thrombin receptor activation peptide induces pulmonary vasoconstriction

1994 ◽  
Vol 266 (2) ◽  
pp. C448-C454 ◽  
Author(s):  
H. Lum ◽  
T. T. Andersen ◽  
J. W. Fenton ◽  
A. B. Malik
Keyword(s):  
Smooth Muscle ◽  
Arterial Pressure ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Pulmonary Arterial Pressure ◽  
Muscle Cells ◽  
Receptor Activation ◽  
Thrombin Receptor ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial

We investigated the involvement of the 14-residue thrombin receptor activating peptide SFLLRNPNDKYEPF (TRAP-14) in mediating the pulmonary vasoconstriction in response to alpha-thrombin. Isolated guinea pig lungs were uniformly perfused with Ringer-albumin solution at a constant flow of 28 ml/min. Addition of TRAP-14 or human alpha-thrombin to the perfusate caused dose-dependent increases of pulmonary arterial pressure within 1 min. TRAP-14 at 1 microM increased pulmonary arterial pressure to a similar extent as 10 nM alpha-thrombin (i.e., increase of 7.7 +/- 0.8 and 7.4 +/- 0.9 cmH2(0) from baseline, respectively). The increases in pulmonary venous resistance induced by TRAP-14 and alpha-thrombin were two- to fivefold greater than the increases in pulmonary arterial resistance, indicating that both agonists mediated pulmonary hypertension secondary to pulmonary venoconstriction. Stimulation of cultured guinea pig pulmonary artery smooth muscle cells with 100 microM TRAP-14 or 10 nM alpha-thrombin increased cytosolic Ca2+ concentration about five- to sevenfold over baseline. The increase in cytosolic Ca2+ concentration in smooth muscle cells was not observed with a subsequent challenge with either agonist, indicating desensitization. In the perfused lungs, an initial stimulation with alpha-thrombin or TRAP-14 desensitized the lungs to either agonist. The alpha-thrombin-desensitized lungs remained refractile to alpha-thrombin after 1 h of perfusion with fresh Ringer solution, whereas the TRAP-14-desensitized lungs recovered 79% of the vasoconstrictor response by 10 min and 93% of the response by 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

scholarly journals Angiotensin II type 2 receptor activation induces RhoA inhibition through Phosphorylation of its Serine 188 in Vascular Smooth Muscle Cells

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Malvyne Rolli‐Derkinderen ◽  
Christophe Guilluy ◽  
Laurent Loufrani ◽  
Daniel Henrion ◽  
Gervaise Loirand ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Receptor Activation

Surface thrombomodulin modulates thrombin receptor responses on vascular smooth muscle cells

1996 ◽  
Vol 270 (2) ◽  
pp. H603-H609 ◽  
Author(s):  
B. W. Grinnell ◽  
D. T. Berg
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cell Line ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cellular Responses ◽  
Thrombin Receptor ◽  
Mitogenic Response ◽  
Agonist Peptide

Vascular smooth muscle cells produce the proteolytically activated thrombin receptor. Under certain conditions, they have been reported to synthesize thrombomodulin (TM), another thrombin receptor known to convert the specificity of thrombin from cleavage of procoagulant/proinflammatory substrates to the cleavage of the anticoagulant/anti-inflammatory factor protein C. In this study, we examined the role of TM in modulating thrombin-mediated cellular responses. Using a thrombin receptor-positive TM-negative rabbit intimal smooth muscle cell line (RIC), we isolated cells expressing varying levels of functional surface TM after transfection with an expression vector containing the cDNA for full-length TM. The parent RIC (TM negative) line responded to alpha-thrombin and to agonist peptide (SFLLRN-PNDKYEPF; abbreviated SFLL) with both mitogenic response and phosphoinositol release. However, transfected cells producing high levels of TM, equivalent to the level on rabbit aortic endothelial cells, responded to SFLL but not to alpha-thrombin. Whereas alpha-thrombin, SFLL, and the combination of SFLL and thrombin resulted in a mitogenic response in the TM-negative RIC line, the response to the agonist peptide could be blocked by thrombin in the TM-producing cell line. The degree to which thrombin receptor activation was blocked directly correlated with the level of TM on the cell surface, and high levels of thrombin could overcome the inhibitory effect. Our data demonstrate that the coexpression of TM with thrombin receptor on vascular smooth muscle cells can result in a modulation of cellular responses to thrombin, which could control thrombin-induced proliferative events following vessel injury or insult.

Cyclooxygenase-2 induction by bradykinin in aortic vascular smooth muscle cells

2006 ◽  
Vol 290 (1) ◽  
pp. H30-H36 ◽  
Author(s):  
Jorge A. Rodriguez ◽  
Paula De la Cerda ◽  
Eileen Collyer ◽  
Valerie Decap ◽  
Carlos P. Vio ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Receptor Activation ◽  
Atheromatous Plaque ◽  
Protein Levels ◽  
Cox 2

Vascular smooth muscle cell proliferation and migration play an important role in the pathophysiology of several vascular diseases, including atherosclerosis. Prostaglandins that have been implicated in this process are synthesized by two isoforms of cyclooxygenase (COX), with the expression of the regulated COX-2 isoform increased in atherosclerotic plaques. Bradykinin (BK), a vasoactive peptide increased in inflammation, induces the formation of prostaglandins through specific receptor activation. We hypothesized that BK plays an important role in the regulation of COX-2, contributing to the increase in production of prostaglandins in vascular smooth muscle cells. Herein we examined the signaling pathways that participate in the BK regulation of COX-2 protein levels in primary cultured aortic vascular smooth muscle cells. We observed an increase in COX-2 protein levels induced by BK that was maximal at 24 h. This increase was blocked by a B2 kinin receptor antagonist but not a B1 receptor antagonist, suggesting that the B2 receptor is involved in this pathway. In addition, we conclude that the activation of mitogen-activated protein kinases p42/p44, protein kinase C, and nitric oxide synthase is necessary for the increase in COX-2 levels induced by BK because either of the specific inhibitors for these enzymes blocked the effect of BK. Using a similar approach, we further demonstrated that reactive oxygen species and cAMP were not mediators on this pathway. These results suggest that BK activates several intracellular pathways that act in combination to increase COX-2 protein levels. This study suggests a role for BK on the evolution of the atheromatous plaque by virtue of controlling the levels of COX-2.

Human thrombin receptor-activating peptide-induced proliferation of cultured vascular smooth muscle cells exhibits species specificity

1995 ◽  
Vol 35 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Coleen A. McNamara ◽  
Ian J. Sarembock ◽  
Lawrence W. Gimple ◽  
John W. Fenton ◽  
Gary K. Owens
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Species Specificity ◽  
Thrombin Receptor ◽  
Human Thrombin

scholarly journals Origin of molecular species of diacylglycerol induced by bombesin in smooth muscle cells from rabbit rectosigmoid

1998 ◽  
Vol 275 (1) ◽  
pp. G138-G150
Author(s):  
Diego Sbrissa ◽  
Amyia Hajra ◽  
Khalil N. Bitar
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Molecular Species ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Receptor Activation ◽  
Benzoic Anhydride ◽  
Normal Phase Hplc ◽  
Long Time ◽  
Hydrolysis Of

The source of early production of sn-1,2-diacylglycerol (DAG) has for a long time been exclusively linked to hydrolysis of phosphatidylinositol 4,5-diphosphate, which on receptor activation is hydrolyzed into DAG and inositol 1,4,5-trisphosphate. We have investigated the origin of lipid sources of DAG production in smooth muscle cells, in response to contraction induced by peptide agonists. We have performed a quantitative analysis of the molecular species of DAG formed in relation to the known molecular composition of parent phospholipids. The molecular species of phospholipids are sufficiently unique that the phospholipid origin of DAGs and its quantitative contribution to their formation can be measured by HPLC. Cell suspensions (10–15 × 106 cells/ml) from the circular muscle of rabbit rectosigmoid were incubated in the presence of the contractile peptide agonist bombesin (BB) at 10−6 M. Reactions were stopped at different time intervals from 30 s to 4 min. DAGs were extracted, purified by TLC, and benzoylated with benzoic anhydride. The benzoylated DAGs were first purified by TLC and then by normal phase HPLC before they were injected onto a reverse-phase column and eluted isocratically. Furthermore, phospholipids in the lipid extract [phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE)] were purified by TLC and similarly analyzed after hydrolysis to DAGs with phospholipase C (PLC). The DAG molecular species profiles for PI, PC, PS, and PE were all unique. Contraction of cells with BB gave noticeable increases (17–55%) in newly formed DAGs. The major phospholipid source of the newly formed DAGs at 30 s was only ∼30% from PI, and the remainder was from PC. In contrast, after 4 min of BB stimulation, a decrease was seen in newly formed DAGs in the peak specific for PI hydrolysis. The data suggest that BB-induced contraction by activation of PLCs results in hydrolysis of different phospholipids. The DAGs formed as a result are qualitatively and quantitatively distinct. This could be the basis for the kinetically different pattern of sustained contraction observed with BB.

PDGF (alpha)-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse

1999 ◽  
Vol 112 (6) ◽  
pp. 905-915 ◽  
Author(s):  
K.A. Grako ◽  
T. Ochiya ◽  
D. Barritt ◽  
A. Nishiyama ◽  
W.B. Stallcup
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Receptor Activation ◽  
Wild Type ◽  
Aortic Smooth Muscle Cells ◽  
Phenotypic Differences ◽  
Aortic Smooth Muscle ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

A line of null mice has been produced which fails to express the transmembrane chondroitin sulfate proteoglycan NG2. Homozygous NG2 null mice do not exhibit gross phenotypic differences from wild-type mice, suggesting that detailed analyses are required to detect subtle alterations caused by the absence of NG2. Accordingly, dissociated cultures of aortic smooth muscle cells from null mice were compared to parallel cultures from wild-type mice for their ability to proliferate and migrate in response to specific growth factors. Both null and wild-type smooth muscle cells exhibited identical abilities to proliferate and migrate in response to PDGF-BB. In contrast, only the wild-type cells responded to PDGF-AA in both types of assays. NG2 null cells failed to proliferate or migrate in response to PDGF-AA, implying a defect in the signaling cascade normally initiated by activation of the PDGF (alpha)-receptor. In agreement with this idea, activation of the extracellular signal-regulated kinase (ERK) in response to PDGF-AA treatment occured only in wild-type cells. Failure to observe autophosphorylation of the PDGF (alpha)-receptor in PDGF-AA-treated null cells indicates that the absence of NG2 causes a defect in signal transduction at the level of (alpha)-receptor activation.

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