Endothelium‐dependent contractile actions of proteinase‐activated receptor‐2‐activating peptides in human umbilical vein: release of a contracting factor <i>via</i> a novel receptor

Saifeddine, Mahmoud; Roy, Samir; Al‐Ani, Bahjat; Triggle, Chris R.; Hollenberg, Morley D.

doi:10.1038/sj.bjp.0702213

Cited by 45 publications

(38 citation statements)

References 30 publications

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“…An endothelium-independent direct contractile e ect on the rabbit aorta (Komuro et al, 1997) and the endothelium-dependent contraction in the human umbilical vein (Saifeddine et al, 1998) were also reported. However, there has so far been no report on direct relaxation.…”

Section: British Journal Of Pharmacology Vol 134 (4)mentioning

confidence: 90%

Mechanism of trypsin‐induced endothelium‐dependent vasorelaxation in the porcine coronary artery

Nakayama

Hirano

Nishimura

et al. 2001

British J Pharmacology

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1 To investigate the mechanism underlying the trypsin-induced endothelium-dependent relaxation, cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and tension development of smooth muscle were simultaneously monitored in the porcine coronary artery, and [Ca 2+ ] i of in situ endothelial cells were monitored in the porcine aortic valvular strips, using fura-2¯uorometry. 2 During the contraction induced by 30 nM U46619, a thromboxane A 2 analogue, 100 nM trypsin induced a rapid transient signi®cant decrease in both [Ca 2+ ] i (from 67.9+5.1 to 15.7+4.4%) and tension (from 97.5+9.2 to 16.8+3.5%) of smooth muscle only in the presence of endothelium (100% level was assigned to the level obtained with the 118 mM K + -induced contraction). [Ca 2+ ] i and the tension thus returned to the levels prior to the application of trypsin by 5 and 10 min, respectively. 3 The initial phase of this relaxation was partly inhibited by 100 mM N o -nitro-L-arginine (L-NOARG), and was completely inhibited by L-NOARG plus 40 mM K + or L-NOARG plus 100 nM charybdotoxin and 100 nM apamin, while the late phase of the relaxation was inhibited by L-NOARG alone. 4 Trypsin induced a transient [Ca 2+ ] i elevation in the endothelial cells mainly due to the Ca 2+ release from the intracellular stores, at the concentrations (1 ± 100 nM) similar to those required to induce relaxation. 5 In conclusion, trypsin induced an elevation in [Ca 2+ ] i mainly due to Ca 2+ release in endothelial cells, and thereby caused endothelium-dependent relaxation. The early phase of relaxation was due to nitric oxide and hyperpolarizing factors, while the late phase was mainly due to nitric oxide in the porcine coronary artery.

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Section: British Journal Of Pharmacology Vol 134 (4)mentioning

confidence: 90%

Mechanism of trypsin‐induced endothelium‐dependent vasorelaxation in the porcine coronary artery

Nakayama

Hirano

Nishimura

et al. 2001

British J Pharmacology

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“…In support of the latter postulate, we observed an SLIGRL-NH 2 -induced afferent arteriolar vasoconstriction after NO synthase inhibition. Previous studies using other vascular preparations have demonstrated that SLIGRL-NH 2 elicits endothelium-dependent (30,32) and endothelium-independent (23) vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

“…PAR-2 is unique, in that it is activated by trypsin and mast cell-derived tryptase (8,26) but not by thrombin (26). PAR-2 can also be activated by a synthetic peptide corresponding to the enzymatically exposed ligand sequence SLIGRL or SLIGRL-NH 2 (26,(30)(31)(32) and is expressed in vascular and nonvascular smooth muscle (25,31) and in vascular endothelium (22).…”

mentioning

confidence: 99%

PAR-2 elicits afferent arteriolar vasodilation by NO-dependent and NO-independent actions

Trottier

Hollenberg

Wang

et al. 2002

American Journal of Physiology-Renal Physiology

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vated receptors (PARs) are a novel class of G protein-coupled receptors that respond to signals through endogenous proteinases. PAR activation involves enzymatic cleavage of the extracellular NH2-terminal domain and unmasking of a new NH2 terminus, which serves as an anchored ligand to activate the receptor. At least four PAR subtypes have been identified. In the present study, we used the in vitro perfused hydronephrotic rat kidney to examine the effects of activating PAR-2 on the afferent arteriole. The synthetic peptide SLIGRL-NH2, which corresponds to the exposed ligand sequence and selectively activates PAR-2, did not alter basal afferent arteriolar diameter but caused a concentration-dependent vasodilation (3-30 M) of arterioles preconstricted by angiotensin II (0.1 nM). A modified peptide sequence (LSIGRL-NH2, inactive at PAR-2) had no effect. This vasodilation was characterized by an initial transient component followed by a smaller sustained response. A similar pattern of vasodilation was seen when SLIGRL-NH2 was administered to isolated perfused normal rat kidney. The sustained component of the PAR-2-induced afferent arteriolar vasodilation was eliminated by nitric oxide (NO) synthase inhibition (100 M nitro-L-arginine methyl ester). In contrast, the transient vasodilation persisted under these conditions. This transient response was not observed when afferent arterioles were preconstricted with elevated KCl, suggesting involvement of an endothelium-derived hyperpolarizing factor. Finally, RT-PCR revealed the presence of PAR-2 mRNA in isolated afferent arterioles. These findings indicate that PAR-2 is expressed in the afferent arteriole and that its activation elicits afferent arteriolar vasodilation by NO-dependent and NO-independent mechanisms.

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“…Thrombin is able to induce vasospasm 26,27 by activation of protease-activated receptors. 28,29 In fact, inhibition of thrombin with hirudin was shown to limit infarct size in a rabbit coronary ligation model. 30 Microvascular patency and consequently myocardial perfusion are predictors of mortality after thrombolytic therapy 31 and after C,D).…”

Section: Discussionmentioning

confidence: 99%

Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque

Bonderman

Teml

Jakowitsch

et al. 2002

Blood

127

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Defined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.03 ؎ 13.00 pg/cm 2 luminal plaque surface). Active TF was sedimented, indicating that TF was associated with membranes. Coronary blood was drawn from 6 patients undergoing coronary interventions with the distal protection device PercuSurge GuardWire (Traatek, Miami, FL). Fine particulate material that was recovered from coronary blood showed TF activity (corresponding to 91.1 ؎ 62.16 pg/mL authentic TF). To examine the role of TF in acute coronary NR, blood was drawn via a catheter from coronary vessels in 13 patients during NR and after restoration of flow. Mean TF antigen levels were elevated during NR (194.3 ؎ 142.8 pg/mL) as compared with levels after flow restoration (73.27 ؎ 31.90 pg/mL; P ‫؍‬ .02). To dissect the effects of particulate material and purified TF on flow, selective intracoronary injection of atherosclerotic material or purified relipidated TF was performed in a porcine model. TF induced NR in the model, thus strengthening the concept that TF is causal, not just a bystander to atherosclerotic plaque material. The data suggest that active TF is released from dissected coronary atherosclerotic plaque and is one of the factors causing the NR phenomenon. Thus, blood-borne TF in the coronary circulation is a major determinant of flow. (Blood. 2002;99:2794-2800)

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Endothelium‐dependent contractile actions of proteinase‐activated receptor‐2‐activating peptides in human umbilical vein: release of a contracting factor via a novel receptor

Cited by 45 publications

References 30 publications

Mechanism of trypsin‐induced endothelium‐dependent vasorelaxation in the porcine coronary artery

Mechanism of trypsin‐induced endothelium‐dependent vasorelaxation in the porcine coronary artery

PAR-2 elicits afferent arteriolar vasodilation by NO-dependent and NO-independent actions

Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque

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