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131.
Seko T Kato M Kohno H Ono S Hashimura K Takenobu Y Takimizu H Nakai K Maegawa H Katsube N Toda M 《Bioorganic & medicinal chemistry letters》2002,12(17):2267-2269
This study was performed to determine the structure-activity relationships (SAR) of L-cysteine based N-type calcium channel blockers. Basic nitrogen was introduced into the C-terminal lipophilic moiety of L-cysteine with a view toward improvement of its physicochemical properties. L-Cysteine derivative 9 was found to be a potent and selective N-type calcium channel blocker with IC(50) of 0.33 microM in calcium influx assay using IMR-32 cells and was 15-fold selective for N-type calcium channels over L-type channels. Compound 9 showed improved oral analgesic efficacy in the rat formalin induced pain model and the rat chronic constriction injury (CCI) model, which is one of the most reliable models of chronic neuropathic pain, without any significant effect on blood pressure or neurological behavior. 相似文献
132.
Differential recognition of tyrosine-based basolateral signals by AP-1B subunit mu1B in polarized epithelial cells 总被引:6,自引:0,他引:6
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Sugimoto H Sugahara M Fölsch H Koide Y Nakatsu F Tanaka N Nishimura T Furukawa M Mullins C Nakamura N Mellman I Ohno H 《Molecular biology of the cell》2002,13(7):2374-2382
To investigate the importance of tyrosine recognition by the AP-1B clathrin adaptor subunit mu1B for basolateral sorting of integral membrane proteins in polarized epithelial cells, we have produced and characterized a mutant form of mu1B. The mutant (M-mu1B) contains alanine substitutions of each of the four conserved residues, which in the AP-2 adaptor subunit micro2 are critical for interacting with tyrosine-based endocytosis signals. We show M-mu1B is defective for tyrosine binding in vitro, but is nevertheless incorporated into AP-1 complexes in transfected cells. Using LLC-PK1 cells expressing either wild type or M-mu1B, we find that there is inefficient basolateral expression of membrane proteins whose basolateral targeting signals share critical tyrosines with signals for endocytosis. In contrast, membrane proteins whose basolateral targeting signals are distinct from their endocytosis signals (transferrin and low-density lipoprotein receptors) accumulate at the basolateral domain normally, although in a manner that is strictly dependent on mu1B or M-mu1B expression. Our results suggest that mu1B interacts with different classes of basolateral targeting signals in distinct ways. 相似文献
133.
Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two orphan G-protein-coupled receptors 总被引:8,自引:0,他引:8
Masuda Y Takatsu Y Terao Y Kumano S Ishibashi Y Suenaga M Abe M Fukusumi S Watanabe T Shintani Y Yamada T Hinuma S Inatomi N Ohtaki T Onda H Fujino M 《Biochemical and biophysical research communications》2002,293(1):396-402
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF, identical to prokineticin 1) is a novel peptide recently identified as a selective mitogen for endocrine gland endothelial cells. The present study demonstrates that EG-VEGF/prokineticin 1 and a peptide closely related to EG-VEGF, prokineticin 2, are cognate ligands of two orphan G-protein-coupled receptors designated ZAQ (=EG-VEGF/PK-R1) and I5E (=EG-VEGF/PK-R2). EG-VEGF/prokineticin 1 and prokineticin 2 induced a transient increase in intracellular calcium ion concentration ([Ca(2+)](i)) with nanomolar potency in Chinese hamster ovary (CHO) cells expressing EG-VEGF/PK-R1 and -R2 and bind to these cells with high affinity and with different receptor selectivity. EG-VEGF/prokineticins provoke rapid phosphorylation of p44/42 MAP kinase and DNA synthesis in the bovine adrenal capillary endothelial cells (BACE). The mRNAs of both EG-VEGF/PK-R1 and -R2 were expressed in BACE. The identification of the receptors for EG-VEGF/prokineticins may provide a novel molecular basis for the regulation of angiogenesis in endocrine glands. 相似文献
134.
Alkaline nitrobenzene oxidation, ozonation and methoxyl content determinations were applied to decomposing leaf litter of Ginkgo biloba L., Cinnamomum camphora sieb., Zelkova serrata Makino and Firmiana simplex W. F. Wight, respectively, during mulching to investigate the properties and estimate changes in lignin composition and content. Since the Klason lignin residue originated from components highly resistant to degradation by acid, the methoxyl content of Klason residue was used to estimate the lignin content of leaf litter. Quantitative analysis of presumed lignin-derived fragments, by use of alkaline nitrobenzene oxidation and ozonation methods, suggested that the estimated lignin content approximates that of the real lignin content of leaves, which is greatly overestimated by the Klason procedure. The estimated lignin contents ranged from 3.9 to 10.0% while the Klason lignan residue varied from 37.1 to 46.7% in un-mulched leaf litter. The absolute amounts of the measured lignin somewhat decreased during mulching, while the structure of lignin remaining in leaf litters after mulching was considered not to be very different from its original structure. 相似文献
135.
Kawakami T Nagata T Muraguchi A Nishimura T 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,787(1):223-229
Apoptosis is an essential process for selection of T lymphocytes specific for foreign antigen in the process of mammalian thymus maturation. Proteomics, a comprehensive study of proteins expressed in a cell, will facilitate the systematic analysis of protein molecules related to such a complicated biological system. Protein expression profiles including information about protein signatures, localization and their quantitative changes with extracellular stimulations are extremely useful to construct intracellular pathway models resulting in the apoptotic cell death. 相似文献
136.
Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia 总被引:27,自引:0,他引:27
Matsunaga T Takemoto N Sato T Takimoto R Tanaka I Fujimi A Akiyama T Kuroda H Kawano Y Kobune M Kato J Hirayama Y Sakamaki S Kohda K Miyake K Niitsu Y 《Nature medicine》2003,9(9):1158-1165
Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis. 相似文献
137.
Tachibana T Matsumoto M Furuse M Hasegawa S Yoshizawa F Sugahara K 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2003,134(4):777-781
We investigated the effect of central and peripheral glucagon-like peptide-1 (GLP-1) on crop emptying in growing chicks. Intracerebroventricular injection of two concentrations of GLP-1 (15 and 60 pmol) similarly suppressed crop emptying, compared with control chicks. The delay in crop emptying induced by GLP-1 (15 pmol) was partly attenuated by co-administration with exendin (5-39) (600 pmol), a GLP-1 receptor antagonist, although exendin (5-39) alone did not affect crop emptying. On the other hand, intraperitoneal administration of several doses of GLP-1 (120, 300 and 3000 pmol) did not alter crop emptying. The present study revealed that central, but not peripheral, GLP-1 inhibits crop emptying in chicks. 相似文献
138.
Chiba T Li YH Yamane T Ogikubo O Fukuoka M Arai R Takahashi S Ohtsuka T Ohkubo I Matsui N 《Peptides》2003,24(5):773-778
In order to find the most effective antagonist for dipeptidyl peptidase III degrading enkephalin, we synthesized hemorphin-like pentapeptides with aliphatic or aromatic amino acids at the N-termini, such as VVYPW, LVYPW, IVYPW, YVYPW, FVYPW and WVYPW. Among those pentapeptides, IVYPW and WVYPW showed the strongest inhibitory activity toward rDPP III. The K(i) values of IVYPW and WVYPW were 0.100+/-0.011 and 0.126+/-0.015 microM (mean+/-S.E.), respectively. The order of K(i) values was Ile> or =Trp>Phe> or =Tyr>Leu>Ala>Val>Ser>Gly. rDPP III activity is inhibited in a non-competitive manner by these peptides. The peptide VYPW did not inhibit rDPP III activity, but the sequence is essential for the expression of inhibitory activity. 相似文献
139.
Masahiko?HirataEmail author Mihoko?Nakagawa Harumi?Funakoshi Takuya?Iwamoto Waka?Otozu Daisuke?Kiyota Shirou?Kuroki Kiichi?Fukuyama 《Journal of Ethology》2003,21(2):161-168
Distance between dam and offspring (1–121 days old) in a herd of Japanese Black cattle (Bos taurus) grazing a tropical grass (Paspalum notatum) pasture (1.5 ha) was investigated during 7-h grazing periods over grazing seasons from May (spring) to October (autumn).
The mother–young distance was not constant throughout the grazing period, repeatedly increasing and decreasing. Although significant
periodicity was always detected in the mother–young distance, there was no consistent dominant cycle, indicating the complexity
of the within-day pattern of mother–young distance. The mean mother–young distance over the grazing period increased as a
calf aged, reaching a plateau at an age of about 33 days. The mean distance of a calf from its mother was usually shorter
than that from a non-mother cow, with the difference between the mean distances decreasing sharply until a calf became about
35 days old. The results and literature show that mutual independence of mother and young rapidly develops in the first 30–50 days
after parturition.
Electronic Publication 相似文献
140.
The effects of dioecy on community dynamics were examined by using transition matrix models for two dioecious tree species, one a superior competitor with a narrow dispersal range and the other an inferior competitor with a wide dispersal range. The models are based on tree-by-tree replacements in each identical microsite occupied by either male or female canopy trees of the superior competitor and canopy trees of the inferior competitor. Coexistence of the two species is possible not only because of a trade-off between competitive and dispersal abilities but also because of the existence of a competitor gap, which the superior competitor cannot occupy. The competitor gap is created under the male trees of the superior competitor. The inferior competitor occupies the competitor gap because of its wide dispersal range. The relative abundance of the two species depends on the dispersal ability and sex ratios of the superior competitor. The decreasing dispersal ability and the female abundance of the superior competitor increase the competitor gap, which allows the regeneration of the inferior competitor.An erratum to this article can be found at 相似文献