Biomedical subjects

K Momose

Publications and source records attributed to K Momose.

At least 55 records · Page 3Linked to original sources

PubMed1998

Stimulation of nitric oxide synthase during oxidative endothelial cell injury.

The purpose of this study was to determine changes in nitric oxide synthase (NOS) activity during the process of lethal oxidative cell injury following H2O2 treatment of endothelial cells. NOS activity was determined by measuring the conversion of [3H]arginine ([3H]Arg) to [3H]citrulline ([3H]Cit). Cell death was assessed by measuring the release of intracellular lactate dehydrogenase (LDH). Moreover, cell death and changes in cytosolic free Ca2+ (Ca(i)2+) were measured simultaneously using a confocal laser scanning system, and propidium iodide and fluo-3 as fluorescent indicators, respectively. Treatment with H2O2 (125-1000 microM) concentration dependently increased L-Cit formation from L-Arg, and a peak was obtained at 90 min after the addition of 500 or 1000 microM H2O2. The H2O2-induced increase in L-Cit formation was blocked completely by N(G)-nitro-L-arginine (L-NNA) or N(G)-methyl-L-arginine (L-NMA), both inhibitors of NOS. LDH release from endothelial cells was evoked from 120 min after the addition of H2O2 (125-1000 microM) in a concentration-dependent manner. Moreover, H2O2 increased Ca(i)2+ before cell death, and addition of Ca2+ chelator inhibited both the increase in L-Cit formation and LDH release by H2O2. The H2O2-induced LDH release was reduced by L-NNA, but not by L-NMA. These results suggest that H2O2 treatment of endothelial cells increases Ca(i)2+ before cell death, and stimulates NOS activity. The activation of NOS may be involved in oxidative endothelial cell death.

Animals↗

PubMed1998

Discrepant intracellular pH changes following intracellular Ca2+ increases induced by glutamate and Ca2+ ionophores in rat hippocampal neurons.

We investigated changes in intracellular pH (pHi) in relation to intracellular Ca2+ concentration ([Ca2+]i) in primary cultured hippocampal neurons treated with glutamate. [Ca2+]i and pHi were imaged with fluorescent dyes and confocal microscopy. Exposure to 1 mM glutamate for 10 min increased [Ca2+]i and evoked acidosis. These changes persisted for at least 60 min, even after removal of glutamate. The increase in [Ca2+]i and the acidosis were not observed in Ca2+-free solution and were attenuated in the presence of MK-801, an NMDA receptor antagonist. We also found that the increase in [Ca2+]i and acidosis could be induced by addition of Ca2+ to the extracellular solution in the cells pretreated with glutamate in Ca2+-free solution, even if glutamate did not exist in the extracellular solution. On the other hand, ionomycin and Br-A23187, calcium ionophores, increased [Ca2+]i to almost the same level as glutamate and increased pHi. Extracellular Ca2+ was also indispensable for the increase in [Ca2+]i and the alkalosis. These results suggest the followings: 1) intracellular acidosis by glutamate is dependent on the presence of extracellular Ca2+; 2) the acidosis does not result from only the increase in [Ca2+]i; and 3) glutamate induces the irreversible disorder of regulatory mechanisms of [Ca2+]i not only by Ca2+-dependent process, but also by Ca2+-independent process.

Animals↗

PubMed1998

Protective effects of tetrahydrobiopterin against nitric oxide-induced endothelial cell death.

The purpose of this study was to examine whether tetrahydrobiopterin (BH4), one of the cofactors of nitric oxide (NO) synthase, attenuates NO-induced endothelial cell death. S-Nitroso-N-acetyl-DL-penicillamine (SNAP) was used as a NO donor. Endothelial cell death was assessed by the leakage of intracellular lactate dehydrogenase (LDH). Addition of SNAP to endothelial cells time- and concentration-dependently induced endothelial cell death. The SNAP-induced endothelial cell death was strongly reduced by the treatment with carboxy-PTIO, a NO scavenger, or catalase, but not with superoxide dismutase (SOD). Moreover, pretreatment with sepiapterin, a precursor of BH4, increased intracellular BH4 content, and strongly reduced the SNAP-induced endothelial cell death. Both the increase in BH4 content and the protective effects of sepiapterin were prevented by co-pretreatment with N-acetylserotonin (NAS), an inhibitor of BH4 synthesis. These findings suggest that the cytotoxicity of NO released from SNAP involves H2O2 production, and increase in intracellular BH4 content attenuates NO-induced endothelial cell death. Scavenging of H2O2 by BH4 may be at least one of the mechanisms by which BH4 reduces NO-induced endothelial cell death.

Animals↗

PubMed1998

Neuropeptide Y produces anxiety via Y2-type receptors.

In the present study, the effects of intracerebroventricular (ICV) NPY, [Leu31, Pro34]NPY and NPY13-36 have been evaluated with respect to anxiety in mice in the elevated plus maze. NPY had opposing effects on behavior, depending on the doses used. NPY decreased the normal preference for the closed arms of the maze at 0.7 nmol, indicating an anxiolytic effect; however, at 7 pmol NPY further increased the preference for the closed arm, indicating an anxiogenic effect. [Leu31, Pro34]NPY, a Y1-type receptor agonist, significantly reduced the preference for the closed arms at 70 pmol. NPY13-36, a Y2-type receptor agonist, significantly intensified the preference at 20 pmol. It has been demonstrated that NPY produces not only an anxiolytic effect via Y1-type receptors, but also an anxiogenic effect via Y2-type receptors. The time course of these NPY actions are quite different and the anxiogenic effect was observed only shortly after ICV NPY injection.

Animals↗

PubMed1998

Motilin increases food intake in mice.

The effect of motilin on food intake was investigated in nonfood-deprived mice. A significant increase in food intake was observed 1 h after ICV administration of motilin (3 nmol/mouse) and continued for 2 h. This effect was attenuated markedly by the motilin receptor antagonist GM-109 (0.3-3 nmol/mouse) in a dose-related manner. GM-109 alone had no effect on food intake. These results indicate that motilin receptors are present in the brain and may have a role in the regulation of food intake.

Animals↗

PubMed1998

Anxiolytic effect of motilin and reversal with GM-109, a motilin antagonist, in mice.

There have been few reports on the effects of the brain-gut peptide motilin on the central nervous system (CNS). We administered motilin intracerebroventricularly to mice and investigated the effect of motilin on anxiety using an elevated plus-maze. Motilin produced a significant decrease in anxiety with an inverted U-shaped dose response. To determine whether the anxiolytic effect of motilin was mediated via motilin receptors in the brain, the effect of GM-109, a novel motilin receptor antagonist, was investigated. GM-109 showed a significant and dose-dependent antagonism on the motilin-induced anxiolytic effect. GM-109 administered alone had no effect on anxiety. These results suggest that motilin receptors are present in the brain and may have a role in anxiety and emotion.

Animals↗

PubMed1998

Alternations of diacylglycerol kinase in streptozotocin-induced diabetic rats.

Dysfunction of organs has been reported in diabetic rats, suggesting an association with changes in intracellular signal transduction pathways including phosphatidylinositol (PI) turnover. Diacylglycerol (DG) kinase catalyses the phosphorylation of DG, which is considered to play a major physiological role in the metabolism of the intracellular messenger DG. However, no relation between DG kinase activity and any disease in mammalian tissue has been reported to date. In the present study, we investigated whether the changes in DG kinase activity are related to diabetes. Basal resting level of DG kinase activity changed in tissue isolated from diabetic rats. Decreases in resting activity detected in aorta and kidney and agonist-induced responses differed between these tissues. Submaximal increases in basal activity also were detected in vas deferens and hepatocytes. These changes in DG kinase activity resemble the functional changes associated with complications of diabetes, suggesting that changes in PI turnover followed by DG kinase activity are a key element in the complications. It is the first study about the changes in DG kinase activity in mammalian disease.

Animals↗

PubMed1998

Reduction by tetrahydrobiopterin of H2O2-induced endothelial cell injury.

The purpose of this study was to examine the effect of tetrahydrobiopterin, a co-factor of nitric oxide synthase, on H2O2-induced endothelial cell injury. Pretreatment with sepiapterin, a precursor of tetrahydrobiopterin biosynthesis, increased tetrahydrobiopterin content of endothelial cells, and reduced H2O2-induced endothelial cell injury, which was measured by leakage of lactate dehydrogenase. Both the increase in tetrahydrobiopterin content and the protective effect of sepiapterin were prevented by co-pretreatment with N-acetylserotonin, an inhibitor of sepiapterin reductase. Although Ca2+ ionophore ionomycin-induced nitric oxide synthesis was increased by pretreatment with sepiapterin, the protective effect of sepiapterin was not affected by an inhibitor of nitric oxide synthesis. On the other hand, pretreatment with sepiapterin also reduced H2O2-induced rat foetal lung fibroblast cell injury via an increase in tetrahydrobiopterin content, despite rat foetal lung fibroblast cells lacking nitric oxide synthase. Moreover, increase in tetrahydrobiopterin strongly reduced H2O2-induced intracellular oxidative stress. These findings indicate that sepiapterin reduces H2O2-induced endothelial cell injury via an increase in tetrahydrobiopterin content. Although increase in endothelial tetrahydrobiopterin content stimulated nitric oxide production, the protective effect of tetrahydrobiopterin against H2O2-induced endothelial cell injury is unlikely to be related to the stimulation of nitric oxide release from nitric oxide synthase. The protective effect of tetrahydrobiopterin may involve reactive oxygen species-scavenging activity.

Animals↗

PubMed1998

N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride inhibits LPS-induced TNF-alpha production and improves survival in endotoxemic mice.

N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride, was examined for its effect on TNF-alpha production by human myeloid THP-1 cells stimulated with lipopolysaccharide (LPS). N2733 inhibited LPS-induced release of TNF-alpha from THP-1 cells with an IC50 of 11 microM. N2733 did not affect the cell viability at the concentration of 50 microM or 100 microM. This indicates that N2733 is a potent inhibitor for TNF-alpha production without severe cytotoxicity. N2733 was also studied in two murine endotoxin shock models induced with LPS. One model was DBA/2 mice injected with LPS (5.6 mg/kg, i.v.), which increased the serum level of TNF-alpha within 1 hr. Treatment of these mice with N2733 (100 mg/kg x 2, i.p.) decreased the serum level of TNF-alpha significantly. Another model was DBA/2 mice induced with LPS (30 mg/kg, i.v.), which reduced the survival rate to 30% during 7 days. Administrations of 30 mg/kg and 100 mg/kg N2733 (i.v.) restored the survival rates to 60% and 90% respectively. Our data demonstrate that N2733 inhibits LPS-induced TNF-alpha production, and this response is associated with an improvement in the survival rate of endotoxemic mice.

Animals↗

PubMed1998

Role of tetrahydrobiopterin in the function of nitric oxide synthase, and its cytoprotective effect (Review).

This review discusses the role of (6R)-5,6,7,8-tetrahydrobiopterin (H4 biopterin) in the function of nitric oxide synthase (NOS), and the protective effect of H4 biopterin against nitric oxide (NO)- and/or reactive oxygen species-induced cytotoxicity. Although NOS releases NO, which regulates vascular tone and immune surveillance under normal conditions, NOS seems to produce superoxide anion and hydrogen peroxide when H4 biopterin, one of the cofactors, or L-arginine, a substrate, is decreased, suggesting the possibility that NOS is a source of reactive oxygen species under pathological conditions. Moreover, simultaneous release of NO and reactive oxygen species in the presence of suboptimal concentrations of H4 biopterin and/or L-arginine may be highly toxic, since NO reacts with superoxide anion and hydrogen peroxide to form peroxynitrite, singlet oxygen and the hydroxyl radical, which are toxic. An increase in H4 biopterin content in cells obviates NOS dysfunction (production of reactive oxygen species instead of NO) and protects the cells against NOS dysfunction-related cell injury. Moreover, H4 biopterin has a strong scavenging activity for reactive oxygen species, and inhibits thier cytotoxicity. H4 biopterin is also likely to reduce NO-induced cytotoxicity. Thus, H4 biopterin is not only an important regulator of NOS function, but is also an intracellular antioxidant. NO and reactive oxygen species are known to be implicated in the development of many pathological states. It is possible that H4 biopterin could be effective for treating many diseases, such as ischemia-reperfusion injury, inflammation and diabetes mellitus.

Biopterins↗

PubMed1998

Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 1: Hemodynamic effects in normal dogs and dogs with acute heart failure.

Cardiovascular effects of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine), a calcium channel blocker, were investigated in anesthetized normal dogs and dogs with acute heart failure (AHF), and compared with those of nitroglycerin (NTG). In open-chest anesthetized dogs, NIC (0.1-10 micrograms/kg/min i.v.) dose-dependently increased cardiac output (CO) and coronary blood flow as well as decreased mean blood pressure (MBP). NIC had no effect on heart rate (HR) or maximum rate of rise of left ventricular pressure (max. dp/dt). In contrast (0.1-10 micrograms/kg/min i.v.) decreased MBP, but did not change the other cardiovascular parameters. NIC and NTG did not prolong PQ, QRS or QTc intervals. In addition, NIC was effective in the presence of dobutamine. In the anesthetized dog model of ischemic AHF induced by coronary ligation, and ischemia/angiotensin II-induced AHF, NIC (1 and 3 micrograms/kg/min i.v.) increased CO and stroke volume, and reduced total peripheral resistance without decreasing HR or cardiac contractility. Furthermore, in the ischemia/angiotension II-induced AHF model, NIC decreased left ventricular end-diastolic pressure (LVEDP). In contrast, NTG (1-10 micrograms/kg/min i.v.) decreased LVEDP in both AHF models; but did not increase CO. These results suggest that NIC improves hemodynamics in dogs with AHF mainly by reducing afterload without adversely affecting the cardiac contractility or conduction system, while NTG exerts its effect on AHF by reducing preload. NIC injection would thus appear to be beneficial in the treatment of AHF.

Acute Disease↗

PubMed1998

Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 2: Effect on myocardial metabolism.

The effect of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine) on myocardial metabolism was investigated in an experimental model of ischemic acute heart failure (AHF) induced by coronary ligation in anesthetized dogs. The left anterior descending and/or circumflex coronary ligation decreased coronary sinus blood flow (CBF), maximum rate of rise of left ventricular pressure (max. dp/dt), cardiac output (CO) and stroke volume (SV), and increased left ventricular end-diastolic pressure, indicating the development of AHF. In this ischemic AHF model, NIC (3 micrograms/kg/min i.v. infusion for 15 min) increased CBF, CO and SV, and reduced systemic and coronary artery resistances, resulting in the improvement of AHF. During the effective period, NIC decreased myocardial oxygen consumption and the coronary arterio-venous difference of oxygen content, carbon dioxide pressure and pH. At the same time, NIC did not decrease the lactate extraction. These results suggest that NIC improves hemodynamics and the balance of myocardium oxygen supply and demand in dogs with AHF by means of reducing afterload and dilating coronary artery.

Acute Disease↗

PubMed1998

[Spinal anesthesia in a patient with spina bifida occulta].

A 32-year-old woman with spina bifida occulta was scheduled for hemorroidectomy under spinal anesthesia. Preoperatively, computed tomography and magnetic resonance imaging (MRI) were performed. The MRI demonstrated the conus medul laris reaching the L 3 level and a lipoma connected with conus medullaris intrathecally. Spinal anesthesia was done successfully at the L 3-4 interspace using 0.3% dibucaine 1.2 ml with 5% glucose 0.8 ml. Postoperatively she showed no neurologic complications. With exact anatomical findings of MRI, spinal anesthesia can be safely performed for patients with spina bifida occulta.

Adult↗

PubMed1997

Development of flexible ventriculoscope (Yamadori-type VII) and its application to experimental animals.

We developed a new ventriculoscope (Yamadori-type VII), a 2.1 mm calibrated fiberscope with a monopolar coagulator, that can be inserted from the cisterna cerebellomedullaris into the third cerebral ventricle of experimental animals, like dogs. With the improved performance of the neuroendoscope compared to its prototype, Yamadori III, it was possible to inspect clearly and to produce electrocoagulative lesions accurately on any part of the intraventricular structures with minimal injury to nearby vital brain areas.

Animals↗

PubMed1997

Receptor-mediated diacylglycerol kinase translocation dependent on both transient increase in the intracellular calcium concentration and modification by protein kinase C.

Diacylglycerol kinase (DG kinase) is activated by various stimuli in many types of cells. We reported earlier that carbachol (CCh) induced DG kinase translocation from the cytosolic fraction to the membrane fraction in guinea pig taenia coli (Biochem. Pharmacol., 50: 591-599, 1995). In this study, the regulation mechanisms of DG kinase translocation are reported, based on the following findings: 1) CCh sustained an increase in DG kinase in the membrane fraction and a decrease in the cytosolic fraction; 2) blocking calcium influx by removing extracellular calcium did not affect the CCh-induced sustained DG kinase translocation; 3) exposing purified protein kinase C (PKC) to DG kinase increased DG kinase affinity to octylglycoside micelles only with the enzyme extracted from the cytosolic fraction; and 4) CCh-induced DG kinase translocation was reversed by removing CCh, and the serine/threonine phosphatase inhibitor, okadaic acid, blocked the reversal of the translocation. These results suggest that CCh-induced DG kinase translocation is promoted by both a transient increase in intracellular calcium, which may be released from the intracellular store, and by DG kinase phosphorylation by PKC.

Animals↗

PubMed1997

Lysophosphatidic acid sensitizes mechanical stress-induced Ca2+ response via activation of phospholipase C and tyrosine kinase in cultured smooth muscle cells.

We previously reported that lysophosphatidic acid (LPA) sensitized mechanical stress-induced intracellular free Ca2+ concentration response (Biochem. Biophys. Res. Commun. 208, 19-25, 1995). In the present study, the signal transduction pathway of the sensitizing effect of LPA was investigated in cultured longitudinal muscle cells from guinea pig ileum. Suramin, a putative LPA receptor antagonist, did not affect the response in the presence of 30 nM LPA, suggesting that the response is induced via activation of suramin-insensitive LPA receptor. Neither pertussis toxin nor wortmannin inhibited the LPA-sensitized response, indicating that G(i/o)- and phosphatidylinositol 3-kinase (PI3-kinase)-mediated pathways are not involved in the sensitizing effect. C3 ADP ribosyltransferase had no effect on the response, whereas formation of actin-stress fiber in the presence of LPA was completely inhibited, suggesting rho-related cytoskeletal change is not involved in the response. In contrast, a phospholipase C (PLC) inhibitor, U73122, completely inhibited the response, but broad spectrum kinase inhibitors, staurosporine and H7, had no effect on the response. In addition, tyrosine kinase inhibitor, genistein, but not tyrphostin partially inhibited the response. These results suggest that LPA sensitizes the mechanical stress-induced response via activation of PLC, but not protein kinase C. Additionally, tyrphostin-insensitive tyrosine kinase, which is related to other pathway than G(i/o)- and rho-mediated pathways, may be involved in the response.

Actins↗

PubMed1997

Acceleration of oxidative stress-induced endothelial cell death by nitric oxide synthase dysfunction accompanied with decrease in tetrahydrobiopterin content.

The purpose of this study was to examine whether nitric oxide (NO) synthase dysfunction accompanied with decrease in tetrahydrobiopterin (BH4) content increases H2O2-induced endothelial cell death. Endothelial cell death was measured by the release of intracellular lactate dehydrogenase (LDH). Intracellular BH4 content was changed by pretreatment with 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, or pretreatment with sepiapterin, a substrate for the salvage pathway of BH4 synthesis, and the intracellular content was measured by high performance liquid chromatography equipped with a fluorescence detector. Moreover, production of superoxide was detected by a chemiluminescence technique using MCLA, a Cypridina luciferin analogue, for the superoxide-sensitive probe. Pretreatment with DAHP (10 mM) for 24 h decreased intracellular BH4 content to 14% and increased H2O2-induced cell death. The toxic effect of DAHP was reduced by co-pretreatment with sepiapterin (100 microM) or treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mM), an inhibitor of NO synthase, but not by N(G)-methyl-L-arginine (L-NMA, 1 mM), the other inhibitor of NO synthase. Moreover, production of superoxide in endothelial cells induced by Ca2+-ionophore ionomycin (1 microM) increased by the pretreatment with DAHP, and the increase in superoxide production was blocked by L-NAME (1 mM) but not L-NMA (1 mM). Co-pretreatment with sepiapterin decreased the production of superoxide. These findings suggested that dysfunction of NO synthase with a decrease in BH4 content in endothelial cells produced superoxide instead of NO and increased the oxidative stress-induced endothelial cell death.

Animals↗

PubMed1997

Lysophosphatidic acid sensitises Ca2+ influx through mechanosensitive ion channels in cultured lens epithelial cells.

We investigated the effect of lysophosphatidic acid (LPA), a bioactive phospholipid, on the response in cytosolic free Ca2+ concentration ([Ca2+]i) to mechanical stress in cultured bovine lens epithelial cells. Spritzing of bath solution onto cells as mechanical stress caused marked increase in [Ca2+]i in the presence of LPA and this increase was concentration-dependent (1-10 microM), whereas neither addition of LPA alone nor the mechanical stress in the absence of LPA affected [Ca2+]i. The mechanical stress-induced increase in [Ca2+]i in the presence of LPA was inhibited by removing extracellular Ca2+ or by addition of Gd3+, a blocker of mechanosensitive cation channels, but not by nicardipine, thapsigargin, an inhibitor of endoplasmic reticulum-ATPase pump, or U73122, a phospholipase C inhibitor. These results show that LPA sensitises Ca2+ influx through cation-selective mechanosensitive channels, but does not sensitise Ca2+ release from intracellular stores, triggered by changes in mechanical stress. On the other hand, phosphatidic acid had less of a sensitising effect than LPA, and neither lysophosphatidylcholine nor chlorpromazine had any effect. Also Ca2+ mobilising agonists, ATP, histamine and carbachol, did not sensitise Ca2+ response to the mechanical stress. These results show that LPA sensitises mechanoreceptor-linked response in lens epithelial cells, suggesting that it plays a role in the development of cataracts due to increases in [Ca2+]i induced by mechanical stress.

Animals↗