A Novel Long-Acting Prostacyclin Agonist (ONO-1301) With an Angiogenic Effect: Promoting Synthesis of Hepatocyte Growth Factor and Increasing Cyclic AMP Concentration via IP-Receptor Signaling

Uchida, Takahiro; Hazekawa, Mai; Yoshida, Miyako; Matsumoto, Kunio; Sakai, Yoshiki

doi:10.1254/jphs.13073fp

Cited by 16 publications

(19 citation statements)

References 46 publications

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“…However, in GH 3 cells treated with iloprost, a prostacyclin analog, or chlorotoxin, ARTinduced block of I K(DR) or I Na remained unaffected. Iloprost is known to increase the level of intracellular cyclic AMP through its bindings to prostacyclin receptors [24]. Chlorotoxin can block the activity of Cl -channels.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of ART on I K(DR) was thus scrutinized in cells treated with chlorotoxin (1 μM) or iloprost (100 nM). Chlorotoxin is an inhibitor of Cl -channels, whereas iloprost, a prostacyclin analog, can induce the production of cyclic AMP [24]. However, unexpectedly, for cells preincubated with either chlorotoxin or iloprost, the inhibitory effect of ART on the I-V relationship of I K(DR) remained unaltered (Fig.…”

Section: Effect Of Art On I K(dr) In Cells Preincubated With Chlorotomentioning

confidence: 93%

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Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

Wu³

et al. 2017

Cell Physiol Biochem

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Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH₃) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K⁺ current (I_K(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I_K(DR) with an IC₅₀ value of 11.2 µM and enhanced I_K(DR) inactivation with a K_D value of 14.7 µM. The steady-state inactivation curve of I_K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I_K(DR) in GH₃ cells. ART also decreased the peak amplitude of voltage-gated Na⁺ current (I_Na) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I_Na, was effective at reversing ART-induced prolongation in inactivation time constant of I_Na. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I_K(DR) and I_Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Art On I K(dr) In Cells Preincubated With Chlorotomentioning

confidence: 93%

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

Wu³

et al. 2017

Cell Physiol Biochem

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“…Of a variety of synthetic agonists or antagonists of this cascade that were developed as a drug, ONO-1301 (7,8-dihydro-5-[( E )-[[a-(3-pyridyl)-benzylidene]aminooxy]ethyl]-1-naphthyloxy]acetic acid) was synthesised as a small molecular weight compound having prostacyclin IP receptor agonistic and thromboxane A2 synthase inhibitory activities (Fig. 1) [16–19]. ONO-1301 was initially developed as an anti-platelet drug; however, a number of the basic studies including those from our laboratory documented that a very small dose of ONO-1301 activates endothelial cells, vascular smooth muscle cells and fibroblasts to release multiple pro-angiogenic/anti-inflammatory factors from their cytoplasm [16, 20–23].…”

Section: Introductionmentioning

confidence: 99%

“…ONO-1301 was initially developed as an anti-platelet drug; however, a number of the basic studies including those from our laboratory documented that a very small dose of ONO-1301 activates endothelial cells, vascular smooth muscle cells and fibroblasts to release multiple pro-angiogenic/anti-inflammatory factors from their cytoplasm [16, 20–23]. In addition, ONO-1301 has several theoretical advantages as a drug over other synthetic prostaglandin agonists, such as beraprost, epoprostenol, iloprost or treprostinil, since ONO-1301 has been shown to exert long-lasting prostacyclin activities [16, 24, 25]. Moreover, poly-lactic co -glycolic acid (PLGA)-polymerised form of ONO-1301, ONO-1301SR, was developed to achieve a sustained-release ONO-1301-delivery-system [16, 25].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, ONO-1301 has several theoretical advantages as a drug over other synthetic prostaglandin agonists, such as beraprost, epoprostenol, iloprost or treprostinil, since ONO-1301 has been shown to exert long-lasting prostacyclin activities [16, 24, 25]. Moreover, poly-lactic co -glycolic acid (PLGA)-polymerised form of ONO-1301, ONO-1301SR, was developed to achieve a sustained-release ONO-1301-delivery-system [16, 25]. This review summarises information and knowledge regarding to ONO-1301 and ONO-1301SR as a tissue regeneration-based drug for cardiac disease and proposes prospect of ONO-1301 for new drug in chronic pathologies.

Fig.…”

Section: Introductionmentioning

confidence: 99%

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A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

et al. 2015

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Cardiac failure is a major cause of mortality and morbidity worldwide, since the standard treatment for cardiac failure in the clinical practice is chiefly to focus on removal of insults against the heart or minimisation of additional factors to exacerbate cardiac failure, but not on regeneration of the damaged cardiac tissue. A synthetic prostacyclin agonist, ONO-1301, has been developed as a long-acting drug for acute and chronic pathologies related to regional ischaemia, inflammation and/or interstitial fibrosis by pre-clinical studies. In addition, poly-lactic co-glycolic acid-polymerised form of ONO-1301, ONO-1301SR, was generated to achieve a further sustained release of this drug into the targeted region. This unique reagent has been shown to act on fibroblasts, vascular smooth muscle cells and endothelial cells in the tissue via the prostaglandin IP receptor to exert paracrinal release of multiple protective factors, such as hepatocyte growth factor, vascular endothelial growth factor or stromal cell-derived factor-1, into the adjacent damaged tissue, which is salvaged and/or regenerated as a result. Our laboratory developed a new surgical approach to treat acute and chronic cardiac failure using a variety of animal models, in which ONO-1301SR is directly placed over the cardiac surface to maximise the therapeutic effects and minimise the systemic complications. This review summarises basic and pre-clinical information of ONO-1301 and ONO-1301SR as a new reagent to enhance tissue salvage and/or regeneration, with a particular focus on the therapeutic effects on acute and chronic cardiac failure and underlying mechanisms, to explore a potential in launching the clinical study.

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Nanomedicine-mediated therapeutic approaches for pulmonary arterial hypertension

Mirhadi

Kesharwani

Johnston

et al. 2023

Drug Discovery Today

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A Novel Long-Acting Prostacyclin Agonist (ONO-1301) With an Angiogenic Effect: Promoting Synthesis of Hepatocyte Growth Factor and Increasing Cyclic AMP Concentration via IP-Receptor Signaling

Cited by 16 publications

References 46 publications

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

Nanomedicine-mediated therapeutic approaches for pulmonary arterial hypertension

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