Compensatory Thrombopoietin Production from the Liver and Bone Marrow Stimulates Thrombopoiesis of Living Rat Megakaryocytes in Chronic Renal Failure

Kazama, Itsuro; Endo, Yasuhiro; Toyama, Hiroaki; Ejima, Yutaka; Kurosawa, Shin; Murata, Yuzo; Matsubara, Mitsunobu; Maruyama, Yoshio

doi:10.1159/000333018

Cited by 16 publications

(18 citation statements)

References 28 publications

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“…After mast cells were incubated in these solutions or a solution containing no drug, exocytosis was externally induced by compound 48/80 (Sigma-Aldrich, St. Louis, MO, USA; final concentration 10 µg/ml) [9]. Bright-field images were acquired from randomly selected 0.1-mm 2 fields of view (10 views from 6 of each condition), as described in our previous studies [9,14]. Degranulated mast cells were defined as cells associated with ≥ 8 granules outside the cell membrane, as described previously [15].…”

Section: Methodsmentioning

confidence: 99%

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Baba¹,

Tachi²,

Maruyama³

et al. 2015

Cell Physiol Biochem

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Backgroud/Aims: Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine bears amphiphilic features and is preferentially partitioned into the lipid bilayers of the plasma membrane, it would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of olopatadine and other anti-allergic drugs on the membrane capacitance (Cm) in rat peritoneal mast cells during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Low concentrations of olopatadine (1 or 10 µM) did not significantly affect the GTP-γ-S-induced increase in the Cm. However, 100 µM and 1 mM olopatadine almost totally suppressed the increase in the Cm. Additionally, these doses completely washed out the trapping of the dye on the cell surface, indicating that olopatadine counteracted the membrane surface deformation induced by exocytosis. As shown by electron microscopy, olopatadine generated inward membrane bending in mast cells. Conclusion: This study provides electrophysiological evidence for the first time that olopatadine dose-dependently inhibits the process of exocytosis in rat peritoneal mast cells. Such mast cell stabilizing properties of olopatadine may be attributed to its counteracting effects on the plasma membrane deformation in degranulating mast cells.

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Section: Methodsmentioning

confidence: 99%

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Baba¹,

Tachi²,

Maruyama³

et al. 2015

Cell Physiol Biochem

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“…Briefly, subtotal nephrectomy was performed in male Sprague-Dawley rats weighing 150-180 g (Japan SLC Inc., Shizuoka, Japan), as described in our previous studies [8,14]. Then, the upper 1/3 and lower 1/3 of the right kidney was ligated to induce infarction.…”

Section: Methodsmentioning

confidence: 99%

Benidipine Suppresses in situ Proliferation of Leukocytes and Slows the Progression of Renal Fibrosis in Rat Kidneys with Advanced Chronic Renal Failure

Kazama

Baba²,

Matsubara

et al. 2014

Nephron Exp Nephrol

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Background/Aims: Leukocytes, such as lymphocytes and macrophages, predominantly express delayed rectifier K⁺ channels (Kv1.3) in their plasma membranes. In our previous study, the overexpression of these channels in leukocytes was strongly associated with their proliferation in kidneys and the progression of renal fibrosis in advanced-stage chronic renal failure (CRF). Since benidipine, a long-acting 1,4-dihydropyridine Ca²⁺ channel blocker, is also highly potent as a Kv1.3 channel inhibitor, it could exert therapeutic efficacy in advanced CRF. Methods: Male Sprague-Dawley rats that underwent 5/6 nephrectomy followed by a 14-week recovery period were used as the model of advanced CRF. Benidipine hydrochloride (5 mg/kg) was started at 8 weeks after nephrectomy and orally administered daily for 6 weeks. The histopathological features of the kidneys were examined in vehicle-treated and benidipine-treated CRF rat kidneys. Cellular proliferation of leukocytes and the cortical expression of proinflammatory cytokines were also examined. Results: In CRF rat kidneys, Kv1.3 channels began to be overexpressed in leukocytes as early as 8 weeks after nephrectomy. In the cortical interstitium of benidipine-treated CRF rat kidneys, both immunohistochemistry and real-time PCR demonstrated decreased expression of fibrotic markers. Benidipine treatment significantly reduced the number of proliferating leukocytes within the cortical interstitium and decreased the expression of cell cycle markers and proinflammatory cytokines. Conclusion: This study demonstrated for the first time that benidipine slowed the progression of renal fibrosis in rat kidneys with advanced CRF. Kv1.3 channels overexpressed in leukocytes were thought to be the most likely therapeutic targets of benidipine in decreasing the number of proliferating leukocytes and repressing the production of inflammatory cytokines.

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“…We conducted standard whole-cell patch-clamp recordings using an EPC-9 patch-clamp amplifier system (HEKA Electronics, Lambrecht, Germany) as described previously [17,23]. The patch pipette resistance was 4-6 MΩ when filled with internal (patch pipette) solution containing (in mM): K-glutamate, 145; MgCl 2 , 2.0; Hepes, 5.0 (pH 7.2 adjusted with KOH).…”

Section: Methodsmentioning

confidence: 99%

“…Bright-field images were acquired from randomly selected 0.1-mm 2 fields of view (10 views from 6 of each condition), as described in our previous study [23]. Degranulated mast cells were defined as cells associated with ≥ 8 granules outside the cell membrane as described previously [13].…”

Section: Methodsmentioning

confidence: 99%

Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

Kazama

Maruyama²,

Takahashi³

et al. 2013

Cell Physiol Biochem

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Background/Aims: Salicylate and chlorpromazine exert differential effects on the chemokine release from mast cells. Since these drugs are amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membranes, they would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate and chlorpromazine on the membrane capacitance (Cm) during exocytosis in rat peritoneal mast cells. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on plasma membrane deformation of the cells. Results: Salicylate dramatically accelerated the GTP-γ-S-induced increase in the Cm immediately after its application, whereas chlorpromazine significantly suppressed the increase. Treatment with salicylate increased the trapping of the dye on the cell surface, while treatment with chlorpromazine completely washed it out, indicating that both drugs induced membrane surface deformation in mast cells. Conclusion: This study demonstrated for the first time that membrane amphipaths, such as salicylate and chlorpromazine, may oppositely modulate the process of exocytosis in mast cells, as detected by the changes in the Cm. The plasma membrane deformation induced by the drugs was thought to be responsible for their differential effects.

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Compensatory Thrombopoietin Production from the Liver and Bone Marrow Stimulates Thrombopoiesis of Living Rat Megakaryocytes in Chronic Renal Failure

Cited by 16 publications

References 28 publications

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Benidipine Suppresses in situ Proliferation of Leukocytes and Slows the Progression of Renal Fibrosis in Rat Kidneys with Advanced Chronic Renal Failure

Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

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