Role of Rho-Associated Protein Kinase and Histamine in Lysophosphatidic Acid-Induced Airway Hyperresponsiveness in Guinea Pigs

Hashimoto, Terumasa; Nakano, Yuuki; Yamashita, Miyuki; Fang, Yang-Il; Ohata, Hisayuki; Momose, Kazutaka

doi:10.1254/jjp.88.256

Cited by 25 publications

(28 citation statements)

References 25 publications

(21 reference statements)

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“…The effect of lysophosphosphatidic acid, a known activator of ROCK, is shown for comparison. [33][34][35] Inactivation of MYPT1 by 5-HT was inhibited by the ROCK inhibitor, Y27632, in a dose-dependent manner ( Figure 1B). Bovine pulmonary artery SMC contain both SERT and a variety of 5-HT receptors, including the 5-HT1B/1D receptor as determined by polymerase chain reaction (unpublished data).…”

Section: -Ht Activates Rockmentioning

confidence: 96%

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

Liu

Suzuki

Day

et al. 2004

Circulation Research

178

160

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Abstract-There is now considerable evidence supporting a mitogenic action of serotonin (5-HT) on vascular smooth muscle cells (SMC) that might participate in pulmonary hypertension (PH). Our previous studies have demonstrated that 5-HT-induced proliferation depends on the generation of reactive oxygen species and activation of extracellular signal-regulated kinase (ERK) 1/ERK2. Activation of Rho kinase (ROCK) in SMC also may be important in PH. We undertook the present study to assess the role of Rho A/ROCK and its possible relation to ERK1/ERK2 in 5-HT-induced pulmonary artery SMC proliferation. We found that this stimulation of SMC proliferation requires Rho A/ROCK as inhibition with Y27632, a ROCK inhibitor, or dominant negative (DN) mutant Rho A blocks 5-HT-induced proliferation, cyclin D1 expression, phosphorylation of Elk, and the DNA binding of transcription factors, Egr-1 and GATA-4. 5-HT activated ROCK, and the activation was blocked by GR 55562 and GR127935, 5-HT 1B/1D receptor antagonists, but not by serotonin transport ( Key Words: smooth muscle cells Ⅲ serotonin Ⅲ Rho kinase Ⅲ ERK1/ERK2 Ⅲ pulmonary hypertension I n addition to its actions as a vasoconstrictor and neurotransmitter, serotonin (5-HT) is now recognized to be a cellular mitogen. [1][2][3] There is evidence that this mitogenic action is initiated by active transport via a cell surface transporter (SERT) of bovine, rat, and human pulmonary vascular smooth muscle cells (SMC). 1,4 -6 For other cells, the mitogenic action might be started through 1 or more of the cell surface receptors for 5-HT. A hierarchy of cell signaling responses occurs subsequent to ligation of the cell surface transporter or receptor. It has been well-established that these signaling responses include sequential activations of the small GTPase coupled protein, Rac-1, NADPH oxidase producing superoxide that is dismutated to H 2 O 2 , and extracellular signal-regulated kinase (ERK) 1/ERK2 MAP kinase. 2,[7][8][9] The small GTPase Rho A and its effector, Rho kinase (ROCK), also participate in cellular stress fiber formation and cell cycle progression. 10 -19 There has been limited study of the relationship of Rho A and ROCK to 5-HT. One study showed that Rho A bound to GTP is elevated in the rabbit aortic vascular ring preparation treated with 5-HT. 20 Another study suggested the activation of Rho A and ROCK in 5-HT-induced contraction of the bovine middle cerebral artery. 21 Serotonin participates in pulmonary hypertension, 5,22,23 and a polymorphism of the 5-HT transporter has been proposed to be involved in pulmonary hypertension in humans. 24 Because agents that block ROCK are currently available 25,26 and may be useful in pulmonary hypertension, 27-29 we have undertaken an investigation of the potential participation of ROCK in pulmonary arterial SMC signaling and proliferation produced by 5-HT. The results of our study show that ROCK is activated by 5-HT and that its activation is essential for SMC proliferation produced by 5-HT. Furthermore, with the use of a chemi...

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Section: -Ht Activates Rockmentioning

confidence: 96%

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

Liu

Suzuki

Day

et al. 2004

Circulation Research

178

160

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“…In contrast, LPA 1 and LPA 2 showed broad ligand specificity (9). We also reported that differential activation by LPA species was evident in airway responsiveness to acetylcholine; furthermore, LPA-induced airway hyperresponsiveness was attributable to histamine release (10). From these points, we also hypothesize that LPA-indiced histamine release may occur via an LPA receptor(s).…”

Section: Introductionmentioning

confidence: 77%

Lysophosphatidic Acid (LPA) Induces Plasma Exudation and Histamine Release in Mice via LPA Receptors

2006

Self Cite

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Abstract. Lysophosphatidic acid (LPA), the simplest of the water-soluble phospholipids, can evoke various biological responses. The present study examined the activity of LPA to induce plasma exudation and histamine release in mice. Plasma exudation was assessed by extravasation of Evans blue. Subcutaneous administration of LPA (1 -100 µg / site) led to increased plasma exudation in the skin. The LPA-induced plasma exudation was inhibited by ketotifen, a histamine H 1 -receptor antagonist, and diacylglycerol pyrophosphate (DGPP), a LPA 1 / LPA 3 -receptor antagonist. Moreover, pretreatment with pertussis toxin and DGPP inhibited the histamine release from peritoneal mast cells induced by LPA. These findings indicate that plasma exudation induced by LPA is mediated by histamine release from mast cells via LPA receptor(s), presumably LPA 1 and / or LPA 3 , coupled to G i / o proteins. Moreover, these findings point to a role of LPA in the pathomechanisms of various allergic disorders.

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“…Initial studies in that area begin in the late 1970s and have started by looking at the combined effect of spasmogens on different measures of lung function in animals (45,46,57,99,102,112,131,152,180,181,192,208,209,224,244), as well as in humans (49,68,97,101,110,156,158,194,202,240). Apart from an interactive synergism at the level of ASM contraction, many other factors can account for these in vivo interactive synergisms.…”

Section: Interactive Synergisms Between Spasmogensmentioning

confidence: 99%

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

Bossé¹,

Paré²,

Boss³

2012

Lung Diseases - Selected State of the Art Reviews

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Role of Rho-Associated Protein Kinase and Histamine in Lysophosphatidic Acid-Induced Airway Hyperresponsiveness in Guinea Pigs

Cited by 25 publications

References 25 publications

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

Lysophosphatidic Acid (LPA) Induces Plasma Exudation and Histamine Release in Mice via LPA Receptors

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

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