The involvement of a novel mechanism distinct from the thrombin receptor in the vasocontraction induced by trypsin

Komuro, Taro; Miwa, Soichi; Minowa, Tetsuya; Okamoto, Yasuo; Enoki, Taijiro; Ninomiya, Haruaki; Zhang, Xiaofeng; Uemura, Yoshiaki; Kikuchi, Hiroe; Masaki, Τοmoh

doi:10.1038/sj.bjp.0701003

Cited by 23 publications

(7 citation statements)

References 33 publications

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“…A high specificity of the receptors for trypsin was also revealed in our experiments showing no after-effects of chymotrypsin or thrombin on the trypsin response ( fig. 8) which supports the notion of different trypsin and thrombin receptors [20]. The endogenous trypsin receptor in the oolemma of Xenopus oocytes, described in our study, might be related to the recently cloned proteolytically activated receptor PAR-2 [21], because both receptors are coupled to G proteins, and they are activated by trypsin but not by thrombin.…”

Section: Discussionsupporting

confidence: 58%

Endogenous trypsin receptors in Xenopus oocytes: linkage to internal calcium stores

Schultheiß

Neumcke

Richter

1997

CMLS, Cell. mol. life sci.

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The effects of the protease trypsin, externally applied to full-grown oocytes of Xenopus laevis, were studied using electrophysiology and fluorometry. The following results were obtained: trypsin in concentrations of 0.1 microgram/ml to 1 mg/ml liberated Ca2+ from internal stores and evoked large transient currents of up to 5 microA in bath solutions containing 1 mM or no Ca2+. The response desensitized for 50 minutes and recovered at longer times. Transient currents could also be elicited by tryptic impurities in commercially available collagenase used for defolliculation of oocytes. Application of chymotrypsin (0.01 or 1 mg/ml) or of thrombin (3.4 ng/ml or 0.34 mg/ml) neither evoked currents nor desensitized trypsin responses. Incubation with 1 microgram/ml Pertussis toxin for 20 to 25 hours prevented the Ca2+ release from internal stores and the activation of transient currents by trypsin. We propose that endogenous receptors in the oolemma, specific for trypsin, are linked to internal Ca2+ stores via Pertussis toxin-sensitive G proteins. Thus, receptor activation by external trypsin raises internal Ca2+ and thereby opens Ca(2+)-activated Cl channels in the oolemma.

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Section: Discussionsupporting

confidence: 58%

Endogenous trypsin receptors in Xenopus oocytes: linkage to internal calcium stores

Schultheiß

Neumcke

Richter

1997

CMLS, Cell. mol. life sci.

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“…20,22 In comparison, PAR-2 peptides had been shown to cause transient contraction of rat gastric smooth muscle, 20 and trypsin has recently been shown to cause contraction of denuded rabbit aorta, even after desensitization with thrombin. 37 These apparently contradictory observations leave open the question of whether functional PAR-2 is present in vascular smooth muscle. We were interested in identifying whether PAR-2 is expressed in human vascular smooth muscle and, if so, determining whether it is functional.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Functional Protease-Activated Receptor-2 (PAR-2) in Human Vascular Smooth Muscle Cells

Molino

Raghunath

Kuo

et al. 1998

ATVB

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Abstract-The protease-activated family of G protein-coupled receptors includes PAR-1 and PAR-3, which are activated by thrombin, and PAR-2, which is activated by trypsin and tryptase. PAR-2 has recently been shown to be expressed in human endothelial cells. In the present studies, we have examined the expression of PAR-2 in other cells, particularly vascular smooth muscle, and tested whether the receptors are functional. The results show that PAR-2 is present in human aorta and coronary artery smooth muscle cells, as well as in arteries traversing the walls of the small intestine. It was also detected in human keratinocytes, sweat glands, intestinal smooth muscle, and intestinal epithelium, but not at all in myocardial smooth muscle and only inconsistently in intestinal veins and venules. Activation of aortic smooth muscle cells in culture with PAR-2 peptide agonists caused a transient increase in the cytosolic Ca 2ϩ concentration. In contrast, PAR-2 mRNA could not be detected in saphenous vein smooth muscle cells, and the same cells placed in culture showed little, if any, response to the PAR-2 agonist peptides. These observations show that PAR-2 is widely distributed in human vascular smooth muscle, particularly in arteries. However, this is not a universal finding and at least some venous smooth muscle cells, including those in saphenous veins, apparently do not express the receptor in detectable amounts. (Arterioscler Thromb Vasc Biol. 1998;18:825-832.)

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“…Under physiological conditions, PAR-1 and PAR-2 are considered to mainly mediate endothelium-dependent relaxation in many types of blood vessels. The direct contractile effect has been reported with certain type of vessels, such as the guinea pig aorta, rabbit aorta, and canine coronary artery, under physiological conditions (18,21,25,27,35). It may thus play a more important role under pathological conditions, partly because PAR-1 and PAR-2 were upregulated in vascular smooth muscle under pathological conditions (8,21,22,37,47).…”

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confidence: 92%

Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury

Fukunaga¹,

Hirano²,

Hirano³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Thrombin and other proteinases exert vascular effects by activating the proteinase-activated receptors (PARs). The expression of PARs has been shown to be upregulated after balloon injury and in human arteriosclerosis. However, the relationship between the receptor upregulation and the alteration of vasomotor function remains to be elucidated. We herein demonstrated that the contractile responses to the PAR-1 and PAR-2 agonist were markedly enhanced in the rabbit femoral arteries after balloon injury. Neointimal thickening was established 4 wk after the injury. No histological change was observed in the sham operation, where the saphenous artery was ligated without any balloon injury. The contractile response to K(+) depolarization was significantly attenuated 1 wk after the injury and then partly recovered after 4 wk. Thrombin, PAR-1-activating peptide, trypsin, and PAR-2-activating peptide induced no significant contraction in the control. All these stimulants induced enhanced responses 1 wk after balloon injury. Such enhanced responses were seen 4 wk after the injury, except for thrombin. There was no change in the Ca(2+) sensitivity of the contractile apparatus as evaluated in the permeabilized preparations. PAR-1-activating peptide (100 mumol/l), but no other stimulants, induced an enhanced contraction in the sham operation. The expression of PAR-1 and PAR-2 slightly increased after the sham operation, whereas it markedly and significantly increased after balloon injury. Our observations suggest that balloon injury induced the receptor upregulation, thereby enhancing the contractile response before the establishment of vascular lesions. The local inflammation associated with the sham operation may also contribute to the receptor upregulation.

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The involvement of a novel mechanism distinct from the thrombin receptor in the vasocontraction induced by trypsin

Cited by 23 publications

References 33 publications

Endogenous trypsin receptors in Xenopus oocytes: linkage to internal calcium stores

Endogenous trypsin receptors in Xenopus oocytes: linkage to internal calcium stores

Differential Expression of Functional Protease-Activated Receptor-2 (PAR-2) in Human Vascular Smooth Muscle Cells

Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury

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