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41.
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Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain using immunohistochemistry and calculated the atypical index, comparing with those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride, pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and risperidone, showed high positive atypical index. Zotepine, perospirone, sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol, timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and levomepromazine had negative atypical index like haloperidol. These results suggest that not only so-called atypical antipsychotics, but also several conventional drugs, possess atypical properties. 相似文献
43.
Banskota AH Nguyen NT Tezuka Y Le Tran Q Nobukawa T Kurashige Y Sasahara M Kadota S 《Life sciences》2004,74(22):2781-2792
The effects of secoisolariciresinol (1) and isotaxiresinol (2), two major lignans isolated from the wood of Taxus yunnanensis, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (d-GalN)/lipopolysaccharide (LPS) were investigated in mice. Co-administration of d-GalN (700 mg/kg) and LPS (10 microg/kg) resulted in a typical hepatic apoptosis characterized by DNA fragmentation and the formation of apoptotic bodies. Serum glutamic pyruvic transaminase (sGPT) and glutamic oxaloacetic transaminase (sGOT) levels were also raised at 8 h after d-GalN/LPS intoxication due to a severe necrosis of hepatocytes. Pre-administration of 1 or 2 (50, 10 mg/kg, i.p.) 12 and 1 h before d-GalN/LPS significantly reduced DNA fragmentation and prevented chromatin condensation, apoptotic body formation and hepatitis. Pro-inflammatory cytokines such as TNF-alpha and interferon-gamma (IFN-gamma) secreted from LPS-activated macrophages are important mediators of hepatocyte apoptosis in this model. Pre-treatment with 1 or 2 significantly inhibited the elevation of serum TNF-alpha and IFN-gamma levels. In a separate experiment, both lignans had a significant dose-dependent protective effect on d-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes and TNF-alpha-mediated cell death in murine L929 fibrosarcoma cells. These results indicated that 1 and 2 prevent d-GalN/LPS-induced hepatic injury by inhibiting hepatocyte apoptosis through the blocking of TNF-alpha and IFN-gamma production by activated macrophages and direct inhibition of the apoptosis induced by TNF-alpha. 相似文献
44.
The YIPP (tyrosine-isoleucine-proline-proline, amino acids 319-322) motif within the C-terminal part of the human AT(1) receptor is associated with angiotensin II (AII)-induced activation of the Jak-STAT pathway and phospholipase Cgamma1 phosphorylation. We report here that mutations of the YIPP motif strongly affect ligand-binding to the receptor. We analysed AT(1) receptors of the wild type (WT) and 11 mutants with a FLAG-epitope-tag within their C-terminal portion. Mutations of the "P-P" amino acid sequence of this motif decreased both AII binding and the AII-induced intracellular Ca(2+) transients. Mutant and WT receptors were expressed equally in the cell membrane and were localized within the plasma membrane. These results suggest that the "P-P" amino acid sequence within the YIPP motif is important for AII binding to the AT(1) receptor. 相似文献
45.
Infected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells and uninfected red cells. These phenomena, called sequestration and rosetting, respectively, are involved in both host pathogenesis and parasite survival. This review provides a critical summary of recent advances in the characterization of the molecules of the infected red blood cell involved in adhesion, i.e. parasite-encoded molecules (PfEMP1, MESA, rifins, stevor, clag 9, histidine-rich protein), a modified host membrane protein (band 3) and exofacial exposure of phosphatidylserine, as well as receptors on the endothelium, i.e. thrombospondin, CD36, ICAM-1 (intercellular adhesion molecule), and chondroitin sulfate. 相似文献
46.
Liu Yan; Oiki Shigetoshi; Tsumura Takehiko; Shimizu Takahiro; Okada Yasunobu 《American journal of physiology. Cell physiology》1998,275(2):C343
To study the mechanisms of glibenclamide actions onvolume-sensitive Clchannels, whole cell patch-clamp studies were performed at various pHlevels in human epithelial Intestine 407 cells. Extracellular application of glibenclamide reversibly suppressed volume-sensitive Cl currents in the entirerange of voltage examined (100 to +100 mV) and accelerated thedepolarization-induced inactivation at pH 7.5. When glibenclamide wasapplied from the intracellular side, in contrast, no effect wasobserved. At acidic pH, at which the weak acid glibenclamide existslargely in the uncharged form, the instantaneous current was, in avoltage-independent manner, suppressed by the extracellular drug atmicromolar concentrations without significantly affecting thedepolarization-induced inactivation. At alkaline pH, at which almostall of the drug is in the charged form, glibenclamide speeded theinactivation time course and induced a leftward shift of thesteady-state inactivation curve at much higher concentrations. Thus itis concluded that glibenclamide exerts inhibiting actions onswelling-activated Clchannels from the extracellular side and that the uncharged form ismainly responsible for voltage-independent inhibition of instantaneous currents, whereas the anionic form facilitates voltage-dependent channel inactivation in human epithelial Intestine 407 cells. 相似文献
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Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation 总被引:3,自引:0,他引:3
Zhang Y Li JX Zhao J Wang SZ Pan Y Tanaka K Kadota S 《Bioorganic & medicinal chemistry letters》2005,15(6):1629-1632
Two series of oleanolic acid derivatives were synthesized and their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) induced by 1alpha,25-dihydroxy vitamin D3 was evaluated in a co-culture assay system. The structure-activity relationships, together with electronic structure based on the frontier molecular orbitals, for example, HOMO and LUMO, related to different amino acid substituents were studied. Derivatives with proline or phenylalanine showed a tendency to enhance the inhibitory activity. 相似文献
50.