Research Interests: Biology, Medicine, Hypertension, Blood Pressure, Animals, and 15 moreMale, Cell Fractionation, Oryza Sativa, Endosperm, Plasmids, Peptide, Delivery System, Amino Acid Sequence, Base Sequence, Fusion Protein, Biochemistry and cell biology, Genetically Modified Rice, Glutelin, Molecular Sequence Data, and Antihypertensive agents
The effect of exogenous opioid peptides, gluten exorphins A5 and B5, which were isolated from the enzymatic digest of wheat gluten, on the postprandial insulin level were examined in rats. The oral administration of gluten exorphin A5 at... more
The effect of exogenous opioid peptides, gluten exorphins A5 and B5, which were isolated from the enzymatic digest of wheat gluten, on the postprandial insulin level were examined in rats. The oral administration of gluten exorphin A5 at a dose of 30 mg/kg w. potentiated the postprandial plasma insulin level and the effect was reversed by naloxone. The administration of gluten exorphin B5 showed a similar effect at a higher dose (300 mg/kg w). Furthermore, intravenous administration of gluten exorphin A5 at a dose of 30 mg/kg w. also stimulated the postprandial insulin release. The fact that orally and intravenously administered gluten exorphin A5 stimulates insulin release suggests that it modulates pancreatic endocrine function by the action after the absorption rather than within the the gastrointestinal tract.
Research Interests: Endocrinology, Chemistry, Life Sciences, Medicine, Internal Medicine, and 15 moreBlood Glucose, Insulin, Glucagon, Animals, Male, Gluten, Eating, Rats, Gastrointestinal Tract, Wistar Rats, Amino Acid Sequence, Biochemistry and cell biology, Molecular Sequence Data, Postprandial Lipemia, and Pharmacology and pharmaceutical sciences
Novokinin (Arg-Pro-Leu-Lys-Pro-Trp) is a potent hypotensive peptide previously designed based on the structure of ovokinin(2-7) (Arg-Ala-Asp-His-Pro-Phe), a vasorelaxing and hypotensive peptide derived from ovalbumin. Novokinin exhibited... more
Novokinin (Arg-Pro-Leu-Lys-Pro-Trp) is a potent hypotensive peptide previously designed based on the structure of ovokinin(2-7) (Arg-Ala-Asp-His-Pro-Phe), a vasorelaxing and hypotensive peptide derived from ovalbumin. Novokinin exhibited an affinity for the angiotensin AT(2) receptor (Ki=7.35 microM). Novokinin significantly lowered systolic blood pressure at a dose of 0.03 and 0.1 mg/kg after intravenous and oral administration, respectively, in spontaneously hypertensive rats (SHRs), and the hypotensive activity was blocked by PD123319, an antagonist of the AT(2) receptor. Novokinin lowered blood pressure in C57BL/6J mice after oral administration at a dose of 50 mg/kg. However, in AT(2) receptor-deficient mice, novokinin did not reduce blood pressure. These results demonstrate that the hypotensive activity of novokinin is mediated by the AT(2) receptor. The hypotensive activity of novokinin in SHRs was completely blocked by indomethacin and CAY10441, an inhibitor of cyclooxygenase and an antagonist of the prostaglandin IP receptor, respectively. These suggest that the hypotensive activity is mediated by prostacyclin and the IP receptor downstream of the AT(2) receptor.
Research Interests: Pharmacology, Endocrinology, Chemistry, Medicine, Internal Medicine, and 15 moreHemodynamics, Mice, Blood Pressure, Nitric oxide, Animals, Male, Peptides, Antagonist, Egg Proteins, Imidazoles, Angiotensin II, Antihypertensive agents, Pharmacology and pharmaceutical sciences, Angiotensin, and Cyclooxygenase
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Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), having affinity for the AT(2) receptor, is a potent vasorelaxing and hypotensive peptide designed based on the structure of ovokinin(2-7), a bioactive peptide derived from ovalbumin. Here we show that... more
Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), having affinity for the AT(2) receptor, is a potent vasorelaxing and hypotensive peptide designed based on the structure of ovokinin(2-7), a bioactive peptide derived from ovalbumin. Here we show that intracerebroventricularly (i.c.v.) administered novokinin dose-dependently suppresses food intake at a dose of 30-100 nmol/mouse in fasted conscious mice. Orally administered novokinin (30-100mg/kg) also suppressed food intake. Novokinin suppressed food intake in wild-type and AT(1) receptor-knockout mice but not in AT(2) receptor-knockout mice after i.c.v. or oral administration. Novokinin-induced anorexigenic activity after i.c.v. administration was blocked by indomethacin, a cyclooxygenase inhibitor, or ONO-AE3-208, an antagonist for EP(4) receptor for PGE(2). Taken together, novokinin may suppress food intake via activation of PGE(2)-EP(4), downstream of the AT(2) receptor.
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Research Interests: Endocrinology, Physiology, Chemistry, Medicine, Humans, and 15 moreInternal Medicine, Blood Glucose, Mice, Animals, Peptides, Feeding Behavior, Food intake, Receptor, Protein Binding, Knockout Mice, Angiotensin Converting Enzyme Inhibitors, Bombesin, Serum albumin, Delayed gastric emptying, and Pharmacology and pharmaceutical sciences
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Research Interests: Endocrinology, Chemistry, Medicine, Dogs, Internal Medicine, and 15 moreBlood Pressure, Nitric oxide, Female, Animals, Male, Peptides, Antagonist, Nitric Oxide Synthase, Amino Acid Sequence, Mesenteric Arteries, Muscle Relaxation, Endorphins, Antihypertensive agents, Pharmacology and pharmaceutical sciences, and In Vitro Techniques
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Research Interests: Chemistry, Calcium, Micelle, Phosphorylation, Casein, and 3 morePhosphate, Dephosphorylation, and Bovine milk
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Casoxin D, Tyr-Val-Pro-Phe-Pro-Pro-Phe, is a opioid antagonist/vaso-relaxing peptide derived from human as,-casein t'2~ Like ~-casomorphin, Tyr-Pro-Phe-Pro-Gly-Prolle, peptides having the Tyr-Pro-Phe sequence have opioid activities... more
Casoxin D, Tyr-Val-Pro-Phe-Pro-Pro-Phe, is a opioid antagonist/vaso-relaxing peptide derived from human as,-casein t'2~ Like ~-casomorphin, Tyr-Pro-Phe-Pro-Gly-Prolle, peptides having the Tyr-Pro-Phe sequence have opioid activities 3-5~. Des-Val 2casoxin D, Tyr-Pro-Phe-Pro-Pro-Phe, which also corresponds to the [ProS, PheS] ~casomorphin-6, showed rather ~-selective opioid activity in a guinea-pig ileum assay system. In the canine mesenteric artery, this peptide also showed vaso-relaxing activity and was named casomokinin ?. Among the casomokinin F derivatives, Tyr-ProPhe-Pro-Pro-Trp showed the most potent opioid activity (ICsB = 80 n~). This peptide, however, had no vaso-relaxing activity. Another derivative, Tyr-Pro-Phe-Pro-Pro-Leu showed very potent vaso-relaxing activity (gCsa = 3x10-'IM) but a weak opioid activity (ICs~ = IO~M). This peptide was named casomokinin L. Vaso-relaxing activities of casoxin D and casomokinin F are mediated by bradykinin receptors of the B,-subtype and prostacyclin as a endothelium-derived relaxing factor. The receptor mediating the vaso-relaxing activity of casomokinin L was neither the BInor B2-receptor. Furthermore, the vaso-relaxation by casomokinin L was blocked by the nitro-arginine methylester suggesting the involvement of nitric oxide as an endothelium-derived relaxing factor. Peptides were synthesized according to conventional t-Boc or Fmoc strategies. Opiold activities were measured in the isolated longitudinal muscle-myenteric plexus of the guinea-pig ileum and mouse vas deferens. The binding assay of peptides for opiold receptors from rat brain membranes were performed in the presence of i nM [3HI DAGO or [3H]DADLE. Vaso-relaxing activities of peptides were measured in the isolated preparation of the canine mesenteric artery which had been preconstricted by prostaglandin F2 ~. As expected, des-Val2-casoxin D showed opioid agonist activity in the guinea-pig ileum assay (Table 1). Thus, the opioid agonist peptide was derivatized from antagonist casoxin D. Other peptides having Tyr-Pro-Phe-Pro-Pro sequence also showed opioid agonist activity. Among them, Tyr-Pro-Phe-Pro-Pro-Trp showed the most potent activity. The potencies of Tyr-Pro-Phe-Pro-Pro-Phe and Tyr-Pro-Phe-Pro-Pro-Trp are comparable to that of morphiceptin 6~. These peptides were rather selective for ~receptors (Table 2).
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SummaryThe phosphorylation of different caseins by a number of tyrosine-specific kinases has been studied. The different kinases showed a range of specificities, suggesting differences in recognition mechanisms. The site of... more
SummaryThe phosphorylation of different caseins by a number of tyrosine-specific kinases has been studied. The different kinases showed a range of specificities, suggesting differences in recognition mechanisms. The site of phosphorylation of αs2-casein by one phosphorylase has been identified, and compared with analogous sites in other proteins.
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As a model study to effectively utilize biologically active peptides derived from food proteins, the optimum conditions for the release of inhibitory peptides for the angiotensin-converting enzyme (ACE) were investigated. Peptides which... more
As a model study to effectively utilize biologically active peptides derived from food proteins, the optimum conditions for the release of inhibitory peptides for the angiotensin-converting enzyme (ACE) were investigated. Peptides which showed apparent inhibition of the enzyme were classified into three groups: true inhibitors, substrates and pro-drug type peptides which are converted from the substrates to the true inhibitors in vivo. After intravenous administration, all of these peptides suppressed the blood pressure elevation caused by the angiotensin I injected. After oral administration in spontaneously hypertensive rats (SHR), however, only the true inhibitors and pro-drug type peptides lowered blood pressure. The thermolysin digest of “Katuo-bushi”, dried bonito which contained many kinds of true inhibitors and pro-drug type peptides showed long-lasting anti-hypertensive effects. On the other hand, those obtained by proteases from digestive tracts were ineffective in lowering the blood pressure of SHR after oral administration. Thus, because of its good taste and anti-hypertensive effect, the thermolysin digest of dried bonito is an ideal food stuff for a physiologically functional food.
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The spacecraft Hayabusa, which was launched in 2003, arrived at its destination, asteroid (25143) Itokawa in September 2005. The appearance of Itokawa, a small S-type near Earth asteroids, was totally unexpected. The surface is covered... more
The spacecraft Hayabusa, which was launched in 2003, arrived at its destination, asteroid (25143) Itokawa in September 2005. The appearance of Itokawa, a small S-type near Earth asteroids, was totally unexpected. The surface is covered with a lot of boulders and there are only a few craters on it. It looks like a contact binary asteroid. The surface composition is quite similar to LL-chondrite. The estimated density is 1.9 ± 0.13 (g/cm3), so the macro-porosity is about 40%. This means that Itokawa is a rubble pile object. In Itokawa, we may see such things that are very close to building blocks of asteroids. In this paper, we review the mission and the first scientific results.
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A c-axis oriented single-domain Sm–Ba–Cu–O bulk superconductor 36 mm in diameter was magnetized by the pulsed field magnetization (PFM) method at 30, 35 and 77 K. The trapped field distributions after applying pulsed fields with different... more
A c-axis oriented single-domain Sm–Ba–Cu–O bulk superconductor 36 mm in diameter was magnetized by the pulsed field magnetization (PFM) method at 30, 35 and 77 K. The trapped field distributions after applying pulsed fields with different amplitudes were measured by scanning a Hall sensor 0.5 mm above the surface of the sample. We also measured the time evolution of magnetic fields during the PFM by using an oscilloscope connected to two Hall sensors mounted on the bulk superconductor surface. Fluxes are found to penetrate into the bulk superconductor and to escape from it by choosing passes through the direction inclined at 45° to growth sector boundaries (GSBs) of the sample. At 35 K, the temperature rise of the sample caused by heat generation due to flux motion becomes more substantial than that at 77 K. Thus, flux jumps occurred through the passes and assisted magnetic fluxes to reach rather easily the centre of the bulk superconductor. As a result, the magnetic field necessary for PFM is lower than that to fully magnetize the sample by means of the static zero-field-cooling magnetization method. The optimized multi-PFM with reducing amplitudes, which was specifically referred to as the IMRA technique, turned out to be very effective in achieving excellent trapped field characteristics by PFM at low temperatures. We could achieve a maximum trapped field of 3.6 T together with a well conical trapped field distribution at 30 K.
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Anatomical segregation of the functionally distinct central and peripheral nervous system (CNS and PNS) and the establishment of precise connectivity between them are fundamental in the development of the nervous system. Yet, the... more
Anatomical segregation of the functionally distinct central and peripheral nervous system (CNS and PNS) and the establishment of precise connectivity between them are fundamental in the development of the nervous system. Yet, the mechanisms underlying these processes are poorly understood. We provide evidence here that the signalling between the chemokine SDF-1 and its receptor CXCR4 contributes to the segregation and connection between the CNS and PNS in mice. SDF-1 or CXCR4 knockout mice show mis-positioned PNS boundary cap cells inside the spinal cord, disrupted glial limiting membrane and misrouted peripheral axons. Analysis of knockout mice of the second SDF-1 receptor CXCR7 showed phenotypes that are suggestive of CXCR7 being an integral component of SDF-1 signalling that controls the normal development of the boundary cap cells and the radial glial fibres.
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ABSTRACT Y-Ba-Cu-O (YBCO) single grains have the potential to generate large trapped magnetic fields for engineering applications, and research on the processing and properties of this material has attracted interest world-wide over the... more
ABSTRACT Y-Ba-Cu-O (YBCO) single grains have the potential to generate large trapped magnetic fields for engineering applications, and research on the processing and properties of this material has attracted interest world-wide over the past 20 years. In particular, the introduction of flux pinning centers to the large grain microstructure to improve its current density Jc , and hence trapped field, has been investigated extensively. Y2Ba4CuMOx [Y-2411(M)], where M=Nb , Ta, Mo, W, Ru, Zr, Bi and Ag, has been discovered recently to form very effective flux pinning centers due primarily to its ability to form nano-size inclusions in the superconducting phase matrix. However, the addition of the Y-2411(M) phase to the precursor composition complicates the melt-processing of single grains. The addition of Y2O3 to the precursor composition, however, broadens the growth window of single YBCO grains containing Y-2411 (M). We report an investigation of the microstructures and superconducting properties of single grains of this composition grown by top seeded melt growth (TSMG).
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Research Interests: Chemistry, Biology, Lactation, Immunoprecipitation, Antiserum, and 4 moreCasein, Mammary gland, Sepharose, and Agarose
The consensus HIV infection pathway, although well supported by abundant experimental evidence, fails to account for infection of cells (e.g., neurons) that lack CD4 and/or coreceptors. We present the hypothesis that p24 capsid protein... more
The consensus HIV infection pathway, although well supported by abundant experimental evidence, fails to account for infection of cells (e.g., neurons) that lack CD4 and/or coreceptors. We present the hypothesis that p24 capsid protein laden with RNA may be an alternative virulent agent. A novel mechanism of HIV infection may involve binding of the capsid with membrane receptors, followed by internalization of the capsid-receptor complex. This new pathway suggests novel strategies for antiviral pharmacotherapy.
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The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central δ-opioid receptor not only stimulated normal diet intake but conversely suppressed high-fat... more
The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central δ-opioid receptor not only stimulated normal diet intake but conversely suppressed high-fat diet intake as well. [d-Pen2,5]-enkephalin (DPDPE), an agonist selective for the δ-receptor, increased normal diet intake after central administration to nonfasted male mice. The orexigenic activity of DPDPE was inhibited by blockade of cyclooxygenase (COX)-2, lipocalin-type prostaglandin D synthase (L-PGDS), D-type prostanoid receptor 1 (DP1), and neuropeptide Y (NPY) receptor type 1 (Y1) for PGD2 and NPY, respectively, suggesting that this was mediated by the PGD2-NPY system. In contrast, DPDPE decreased high-fat diet intake in mice fed a high-fat diet. DPDPE-induced suppression of high-fat diet intake was blocked by antagonists of melanocortin 4 (MC4) and corticotropin-releasing factor (CRF) receptors but not by knockout of the L-PGDS gene. Thes...
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We have found various bioactive peptides derived from animal and plant proteins, which interact with receptors for endogenous bioactive peptides such as opioids, neurotensin, complements C3a and C5a, oxytocin, and formyl peptides etc.... more
We have found various bioactive peptides derived from animal and plant proteins, which interact with receptors for endogenous bioactive peptides such as opioids, neurotensin, complements C3a and C5a, oxytocin, and formyl peptides etc. Among them, rubiscolin, a δ opioid peptide derived from plant RuBisCO, showed memory-consolidating, anxiolytic-like, and food intake-modulating effects. Soymorphin, a μ opioid peptide derived from β-conglycinin showed anxiolytic-like, anorexigenic, hypoglycemic, and hypotriglyceridemic effects. β-Lactotensin derived from β-lactoglobulin, the first natural ligand for the NTS2 receptor, showed memory-consolidating, anxiolytic-like, and hypocholesterolemic effects. Weak agonist peptides for the complements C3a and C5a receptors were released from many proteins and exerted various central effects. Peptides showing anxiolytic-like antihypertensive and anti-alopecia effects via different types of receptors such as OT, FPR and AT2 were also obtained. Based on...
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Met-Arg-Trp (MRW) has been isolated as an inhibitor for angiotensin I-converting enzyme (ACE) from a pepsin-pancreatin digest of spinach ribulose bisphosphate carboxylase/oxygenase (Rubisco) (IC(50)=0.6 microM). It has been reported that... more
Met-Arg-Trp (MRW) has been isolated as an inhibitor for angiotensin I-converting enzyme (ACE) from a pepsin-pancreatin digest of spinach ribulose bisphosphate carboxylase/oxygenase (Rubisco) (IC(50)=0.6 microM). It has been reported that hypotensive activity of ACE-inhibitory peptides derived from food proteins are weakened in spontaneously hypertensive rats older than 25 weeks (old SHR). However, MRW reduced blood pressure after oral administration at a dose of 5 mg/kg in old SHR as well as in younger SHR. MRW exhibited vasorelaxing activity above 1 microM in isolated mesenteric artery from adult and old SHR. The vasorelaxing activity of MRW was blocked by indomethacin and BW A868C, a cyclooxygenase inhibitor and an antagonist for DP(1) receptor, respectively. However, N(G)-nitro-L-arginine methyl ester, an inhibitor for nitric oxide synthase, had no effect on the relaxation. The hypotensive activity of MRW was also blocked by indomethacin and BW A868C, respectively, in adult and old SHR. Taken together, the vasorelaxing and hypotensive activities of MRW may be mediated by prostaglandin D(2) and the DP(1) receptor. These findings suggest that the hypotensive activity of MRW is mainly caused by vasorelaxation rather than by ACE-inhibition.
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Previously, we found that orally administered soymetide-4 (MITL), an immunostimulating peptide derived from soybean beta-conglycinin alpha' subunit, suppressed alopecia... more
Previously, we found that orally administered soymetide-4 (MITL), an immunostimulating peptide derived from soybean beta-conglycinin alpha' subunit, suppressed alopecia induced by the anti-cancer drug etoposide in neonatal rats. Soymetide-4 has weak affinity for N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor. fMLP showed an anti-alopecia effect after intraperitoneal administration, though it was inactive after oral administration. Anti-alopecia effect of fMLP was blocked by pyrilamine or cimetidine, antagonists for histamine H1 or H2 receptor, respectively. However, the anti-alopecia effect of soymetide-4 was not inhibited by the histamine antagonists but by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for PGE2. Anti-alopecia effect of soymetide-4 was also blocked by pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB (NF-kappaB). These results suggest that PGE2, which is produced after activation of COX by soymetide-4, might suppress apoptosis of hair matrix cells and etoposide-induced alopecia by activating NF-kappaB.