Mechanisms for modulation of mouse gastrointestinal motility by proteinase-activated receptor (PAR)-1 and -2 in vitro

Sekiguchi, Fumiko; Hasegawa, Naomi; Inoshita, Keiko; Yonezawa, Daiki; Inoi, Naoki; Kanke, Toru; Kawabata, Atsufumi

doi:10.1016/j.lfs.2005.06.035

Cited by 20 publications

(28 citation statements)

References 46 publications

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“…However, some studies have indicated the possibility. For instance, it has been observed in vitro that activation of protease-activated receptors caused increased release of PGs from human intestinal epithelial cells (24) and rat gastric epithelial cells (157,180), whereas PG-dependent contractions induced by the activation of protease-activated receptors have also been observed in rat and mouse stomach (149,156). In addition, LPS, the major component of the outer membrane of bacteria, has also been found to induce PG-dependent intestinal contraction and epithelial release of PGs in the rabbit (145).…”

Section: Gastrointestinal (Gi) Tractmentioning

confidence: 99%

Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

2011

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As an analog to the endothelium situated next to the vascular smooth muscle, the epithelium is emerging as an important regulator of smooth muscle contraction in many vital organs/tissues by interacting with other cell types and releasing epithelium-derived factors, among which prostaglandins have been demonstrated to play a versatile role in governing smooth muscle contraction essential to the physiological and pathophysiological processes in a wide range of organ systems. As widely distributed throughout the body, including the blood vessels, airways, gastrointestinal, urinary, and reproductive tracts, smooth muscles have a variety of critical functions such as controlling blood pressure, respiration, and gastrointestinal peristalsis. Abnormality in smooth muscle contractility results in various disorders and diseases including hypertension, asthma, and dyspepsia (89, 95,179). Therefore, smooth muscle contraction is tightly regulated. Apart from the long-recognized regulation by neurotransmitters released from the innervating nerve endings or hormones from the blood stream nearby (66), smooth muscle contraction has been known, for over three decades, to be regulated by the endothelium lining the blood vessels with nitric oxide (NO) as the most important endothelial-derived factor (51, 121). Over recent decades, evidence has also been accumulated indicating an important role of the epithelium, the cell layer lining the luminal surface of many organs or tracts, such as the trachea/bronchus, stomach, intestine, bladder, and reproductive organs, in the regulation of smooth muscle contraction, with a number of epithelium-derived factors identified. However, the importance of the epithelium in regulating smooth muscle tones has not been adequately appreciated. In this review, we will examine the evidence collected from a number of organ systems and hope to provide a clearer picture as to how the epithelium acts as an indispensable regulator of smooth muscle contraction, with epithelium-derived prostaglandins (PGs) as the key mediators, participating in many vital physiological processes as well as the pathogenesis of many diseases.

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Section: Gastrointestinal (Gi) Tractmentioning

confidence: 99%

Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

2011

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“…Both contractile and relaxant effects of trypsin thus appear to be attributable to a myogenic response. A trypsin-induced biphasic response was also reported in the mouse gastric fundus (Cocks et al, 1999) and small intestine (Kawabata et al, 1999;Sekiguchi et al, 2006). In these studies, the biphasic responses consisted of an initial relaxation followed by a contraction and the relaxant effects were observed at lower concentrations than those required for the contractile effects.…”

Section: Discussionmentioning

confidence: 70%

Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter

Tanaka

Ihara

Hirano

et al. 2015

European Journal of Pharmacology

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The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300nM) induced a transient contraction. At concentrations of 1μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1μM)-induced contractions were partially inhibited by pretreatment with 10μM Y-27632. In addition, trypsin (10μM)-induced relaxation was partially inhibited by pretreatment with 10μM Y-27632, 10μM PD98059 or 10μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K(+) concentration to 40mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10μM glibenclamide or 1μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility.

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“…Modulation of gastrointestinal smooth muscle motility by PAR1, PAR2 and PAR4 has been described in vitro (Cocks et al, 1999b;Kawabata et al, 2000a;Kawabata et al, 1999;Mule et al, 2003;Mule et al, 2004;Saifeddine et al, 1996;Sekiguchi et al, 2006) as well as in vivo (Kawabata et al, 2001b) (Table 1). The underlying mechanisms for the motility modulation by PARs vary with species and the parts of the gastrointestinal tract.…”

Section: Involvement Of Prostanoids In Modulation Of Gastrointestinalmentioning

confidence: 98%

“…It is to note that, like PAR1, PAR2 also modulates gastric mucosal circulation and suppresses gastric acid secretion, whereas the underlying mechanisms do not involve endogenous PGs (Kawabata, 2002;Kawabata et al, 2001a;Kawabata et al, 2003;Nishikawa et al, 2002;Sekiguchi et al, 2004). (Tanaka et al, 2003) Salivary glands Rat sublingual gland PAR2 ↑ Mucin secretion (TK-dependent) (Kawabata et al, 2000b) Rat parotid gland PAR2 ↑ Amylase secretion (NO-dependent) Stomach Rat stomach PAR1 Mucosal protection, ↓ Acid secretion (PGs-dependent) (Kawabata et al, 2004c), ↑ Pepsinogen secretion (Kawao et al, 2003) Mouse stomach PAR2 PAR2 Mucosal protection, ↑ Mucus secretion (sensory neuron-dependent) (Kawabata et al, 2001a), ↓ Acid secretion (Nishikawa et al, 2002), ↑ Pepsinogen secretion (Kawao et al, 2002) Mucosal protection (sensory neuron-dependent) (Kawabata et al, 2005) Rat gastric epithelial cells (RGM1) PAR1 ↑ PGE 2 release (Sekiguchi et al, 2005;Toyoda et al, 2003), ↑ Mucus secretion (Sekiguchi et al, 2005;Toyoda et al, 2003) Pancreas Dog pancreatic duct epithelial cells PAR2 ↑ Cl -and K + secretion ([Ca 2+ ] in ↑-dependent) (Nguyen et al, 1999) Rat pancreas PAR2 ↑ Amylase secretion (NO-dependent) GI motility Mouse GI transit (in vivo) PAR1, PAR2 Facilitation of transit (L-VDCC-dependent) (Kawabata et al, 2001b) Mouse gastric longitudinal muscle PAR1, PAR2 Contraction (PGs and sensory neuron-dependent) (Sekiguchi et al, 2006), Relaxation (SK-dependent) (Cocks et al, 1999b;Sekiguchi et al, 2006) Mouse ileal longitudinal muscle PAR1 Contraction (PGs-dependent), Relaxation (partially SK-dependent) (Sekiguchi et al, 2006) Rat esophageal muscularis mucosa PAR1 Contraction (L-VDCC-dependent) ( …”

Section: Par1-triggered Pge 2 Formation and The Underlying Cell Signamentioning

confidence: 99%

“…The underlying mechanisms for the motility modulation by PARs vary with species and the parts of the gastrointestinal tract. Involvement of contractile PGs has been shown in PAR2-mediated contraction in the gastric longitudinal smooth muscle of rats (Saifeddine et al, 1996) and PAR1-and PAR2-mediated contraction in the gastric and ileal longitudinal smooth muscle of mice (Sekiguchi et al, 2006). The contractile PGs involved in the effects of PAR agonists have yet to be identifi ed.…”

Section: Involvement Of Prostanoids In Modulation Of Gastrointestinalmentioning

confidence: 99%

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Proteinase-activated receptors in the gastrointestinal system: a functional linkage to prostanoids

2007

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Proteinase-activated receptors (PARs), G protein-coupled receptors, play critical roles in the alimentary system. Increasing evidence suggests that endogenous prostaglandins (PGs) mediate some of PARs' gastrointestinal functions. Systemic administration of the PAR1 agonist protects against gastric mucosal injury through PG formation in rats. PGs also appear to contribute, at least in part, to enhancement of gastric mucosal blood flow and suppression of gastric acid secretion by PAR1 activation. There is also evidence for involvement of PGs in modulation of gastrointestinal motility by PAR1 or PAR2. Importantly, modulation of ion transport by PAR1 or PAR2 in the intestinal mucosal epithelium is largely mediated by PGs. Studies using gastric and intestinal mucosal epithelial cell lines imply that the PAR1-triggered formation of PGs involves multiple signaling pathways including Src, EGF receptor trans-activation and activation of MAP kinases. Collectively, a functional linkage of PAR1 and/or PAR2 to PGs is considered important in the gastrointestinal system.

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Mechanisms for modulation of mouse gastrointestinal motility by proteinase-activated receptor (PAR)-1 and -2 in vitro

Cited by 20 publications

References 46 publications

Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter

Proteinase-activated receptors in the gastrointestinal system: a functional linkage to prostanoids

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