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961.
Sonda S Kawahara T Murozono T Sato N Asano K Haga K 《Bioorganic & medicinal chemistry》2003,11(19):4225-4234
A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the 1-position on the piperidine ring was synthesized. They were evaluated for serotonin 4 (5-HT(4)) receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (1a, Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a. These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability. 相似文献
962.
Shiina T Arai K Tanabe S Yoshida N Haga T Nagao T Kurose H 《The Journal of biological chemistry》2001,276(35):33019-33026
beta(1)-Adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. However, beta(1)AR can internalize as G protein-coupled receptor kinase 2 (GRK2) is fused to its carboxyl terminus. Internalization of the beta(1)AR and GRK2 fusion protein (beta(1)AR/GRK2) is dependent on dynamin but independent of beta-arrestin and phosphorylation. The beta(1)AR/GRK2 fusion protein internalizes via clathrin-coated pits and is found to co-localize with the endosome that contains transferrin. The fusion proteins consisting of beta(1)AR and various portions of GRK2 reveal that the residues 498-502 in the carboxyl-terminal domain of GRK2 are critical to promote internalization of the fusion proteins. This domain contains a consensus sequence of a clathrin-binding motif defined as a clathrin box. In vitro binding assays show that the residues 498-502 of GRK2 bind the amino-terminal domain of clathrin heavy chain to almost the same extent as beta-arrestin1. The mutation of the clathrin box in the carboxyl-terminal domain of GRK2 results in the loss of the ability to promote internalization of the fusion protein. GRK2 activity increases and then decreases as the concentration of clathrin heavy chain increases. Taken together, these results imply that GRK2 contains a functional clathrin box and directly interacts with clathrin to modulate its function. 相似文献
963.
Minami T Tohno S Utsumi M Moriwake Y Yamada MO Tohno Y 《Biological trace element research》2001,79(1):29-38
The aim of the present study was to determine variability of aluminum (Al) accumulation in human arteries and to observe the
relationship between Al and five other elements (Ca, Fe, Mg, P, and Si) in the arteries. The Al contents in the thoracic aorta,
basilar, coronary, femoral, and radial arteries of 26 human subjects were estimated by an inductively coupled plasma-atomic
emission spectrometer and compared quantitatively to five elements. Al was detected in 88% of the cases in both the femoral
and radial arteries, 73% in the coronary artery, 58% in the aorta, and 31% in the basilar artery. The average Al content was
highest in the femoral artery (48.3 ± 15.0 μg/g dry weight) and lowest in the basilar artery (8.1 ± 3.6 μg/g). The Al had
positive correlations with P, Ca, or Mg in both the aorta and femoral artery, and with Ca or P in the basilar artery. In the
coronary artery, a correlation was found between Al and Si. No relationships were found between Al and each of the five elements
in the radial artery. From these results, Al varied widely among the five arteries and accumulated more in the femoral and
radial arteries but less in the basilar artery. These accumulations of Al were positively correlated with Ca or P in several
arteries, but not sufficiently to explain the accumulation of Al. Further investigations are required to understand the mechanism
of the variability of Al accumulation in the arteries. 相似文献
964.
Enhancement of the thermophilic stage in cattle waste composting by addition of tofu residue 总被引:1,自引:0,他引:1
The microbial degradation and temperature rise during the composting of a cattle waste and rice straw mixture blended with tofu (soybean curd) residue was investigated using an insulated and unheated in-vessel composter (effective volume, 12 1) and a static pile with passive aeration. The addition of 11% (dry weight basis) of tofu residue shortened the time required for temperature to reach the thermophilic phase and increased the duration of the temperatures above 55 degrees C significantly, but the maximum temperature was not affected by the additive level. As shown by the change in BOD, most of the easily biodegradable matter in the tofu residue was consumed during 12 days of composting. The same results were observed in the temperature profile of the static pile with passive aeration. Tofu residue addition yielded a higher maximum temperature and a nearly two times longer duration of temperatures above 55 degrees C in almost all locations of the pile. The use of tofu residue as a co-composting material would promote thermophilic degradation throughout the entire composting mass. 相似文献
965.
Inhibitory role of endophilin 3 in receptor-mediated endocytosis 总被引:1,自引:0,他引:1
Sugiura H Iwata K Matsuoka M Hayashi H Takemiya T Yasuda S Ichikawa M Yamauchi T Mehlen P Haga T Yamagata K 《The Journal of biological chemistry》2004,279(22):23343-23348
Endophilin 1 (Endo1) participates in synaptic vesicle biogenesis through interactions of its Src homology 3 domain with the polyphosphoinositide phosphatase Synaptojanin and the GTPase Dynamin. Endo1 has also been reported to affect endocytosis by converting membrane curvature via its lysophosphatidic acid acyltransferase activity. Here we report that a closely related isoform of Endo1, Endo3, inhibits clathrin-mediated endocytosis. Mutational analyses showed that the variable region of Endo3 is important in regulating transferrin endocytosis. In the brain, Endo3 is co-localized with dopamine D2 receptor in olfactory nerve terminals and inhibits its clathrin-mediated endocytosis in COS-7 cells. Furthermore, overexpression of Endo3 in an olfactory epithelium-derived cell line suppressed dopamine D2 receptor-mediated endocytosis and therefore accelerated its dopamine-induced differentiation. These results indicate that Endo3 may act as a negative regulator of clathrin-mediated endocytosis in brain neurons. 相似文献
966.
Azuma C Tohno Y Tohno S Moriwake Y Utsumi M Minami T Imada T 《Biological trace element research》2004,101(2):133-145
To elucidate compositional changes of the stomach with aging, the authors investigated age-related changes of the elements and relationships among the elements in the muscular layers of the pylorus, cardia, lesser curvature, and greater curvature by inductively coupled plasma-atomic emission spectrometry. After ordinary dissection by medical students, the pylori, cardias, lesser curvatures, and greater curvatures were removed from the subjects, consisting of 19 men and 1 woman, ranging in age from 65 to 95 yr. The muscular layers were isolated and the element contents were determined.The calcium content increased progressively with aging in the muscular layers of the pylorus, cardia, and lesser curvature, whereas it tended to increase in the muscular layer of the greater curvature with aging. Regarding sulfur, the content increased significantly in the muscular layer of the pylorus with aging, but not significantly in the muscular layers of the cardia, lesser curvature, and greater curvature with aging.Regarding the relationships among the elements, significant direct correlations were found among calcium, phosphorus, sulfur, and magnesium in both the muscular layers of the pylori and cardias, with some exceptions. 相似文献
967.
Yoshida Y Kinuta M Abe T Liang S Araki K Cremona O Di Paolo G Moriyama Y Yasuda T De Camilli P Takei K 《The EMBO journal》2004,23(17):3483-3491
Amphiphysin is a major dynamin-binding partner at the synapse; however, its function in fission is unclear. Incubation of large unilamellar liposomes with mice brain cytosol led to massive formation of small vesicles, whereas cytosol of amphiphysin 1 knockout mice was much less efficient in this reaction. Vesicle formation from large liposomes by purified dynamin was also strongly enhanced by amphiphysin. In the presence of liposomes, amphiphysin strongly affected dynamin GTPase activity and the recruitment of dynamin to the liposomes, but this activity was highly dependent on liposome size. Deletion from amphiphysin of its central proline-rich stretch dramatically potentiated its effect on dynamin, possibly by relieving an inhibitory intramolecular interaction. These results suggest a model in which maturation of endocytic pits correlates with the oligomerization of dynamin with either amphiphysin or other proteins with similar domain structure. Formation of these complexes is coupled to the activation of dynamin GTPase activity, thus explaining how deep invagination of the pit leads to fission. 相似文献
968.
969.
Two distinct signaling pathways participate in auxin-induced swelling of pea epidermal protoplasts 下载免费PDF全文
Protoplast swelling was used to investigate auxin signaling in the growth-limiting stem epidermis. The protoplasts of epidermal cells were isolated from elongating internodes of pea (Pisum sativum). These protoplasts swelled in response to auxin, providing the clearest evidence that the epidermis can directly perceive auxin. The swelling response to the natural auxin IAA showed a biphasic dose response curve but that to the synthetic auxin 1-naphthalene acetic acid (NAA) showed a simple bell-shaped dose response curve. The responses to IAA and NAA were further analyzed using antibodies raised against ABP1 (auxin-binding protein 1), and their dependency on extracellular ions was investigated. Two signaling pathways were resolved for IAA, an ABP1-dependent pathway and an ABP1-independent pathway that is much more sensitive to IAA than the former. The response by the ABP1 pathway was eliminated by anti-ABP1 antibodies, had a higher sensitivity to NAA, and did not depend on extracellular Ca(2+). In contrast, the response by the non-ABP1 pathway was not affected by anti-ABP1 antibodies, had no sensitivity to NAA, and depended on extracellular Ca(2+). The swelling by either pathway required extracellular K(+) and Cl(-). The auxin-induced growth of pea internode segments showed similar response patterns, including the occurrence of two peaks in the dose response curve for IAA and the difference in Ca(2+) requirements. It is suggested that two signaling pathways participate in auxin-induced internode growth and that the non-ABP1 pathway is more likely to be involved in the control of growth by constitutive concentrations of endogenous auxin. 相似文献
970.