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排序方式: 共有867条查询结果,搜索用时 15 毫秒
1.
John W. Wright Anita J. Bechtholt Shelley L. Chambers Joseph W. Harding 《Peptides》1996,17(8):1365-1371
The present investigation determined that native angiotensins II and III (ANG II and III) were equipotent as pressor agents when ICV infused in alert rats, whereas native angiotensin IV (ANG IV) was less potent. An analogue of each of these angiotensins was prepared with a hydroxyethylamine (HEA) amide bond replacement at the N-terminus, yielding additional resistance to degradation. These three angiotensin analogues, HEA-ANG II, HEA-ANG III, and HEA-ANG IV, were equivalent with respect to maximum elevation in pressor responses when ICV infused; and each evidenced significantly extended durations of effect compared with their respective native angiotensin. Comparing analogues, HEA-ANG II had a significantly longer effect compared with HEA-ANG III, and HEA-ANG IV, whereas the latter were equivalent. Pretreatment with the AT1 receptor subtype antagonist, Losartan (DuP753), blocked subsequent pressor responses to each of these analogues, suggesting that these responses were mediated by the AT1 receptor subtype. Pretreatment with the specific AT4 receptor subtype antagonist, Divalinal (HED 1291), failed to influence pressor responses induced by the subsequent infusion of these analogues. These results suggest an important role for Ang III, and perhaps ANG IV, in brain angiotensin pressor responses mediated by the AT1 receptor subtype. 相似文献
2.
Summary The activated dimonophosphate of 3-deoxyadenosine (cordycepin) undergoes oligomerization to produce a new family of pyrophosphate-linked oligomers in which the average repeating unit involves a nine-atom structural group. The presence of a poly(U) template increase the relative yields of higher oligomers, although the template-free reaction is itself extremely efficient.For the previous paper in this series see Schwartz et al. (1987) 相似文献
3.
The effects of structural analogues, excitatory amino acids and certain drugs on spontaneous and potassium-stimulated exogenous taurine and GABA release were investigated in mouse cerebral cortex slices using a superfusion system. Spontaneous efflux of both amino acids was rather slow but could be enhanced by their uptake inhibitors. Taurine efflux was facilitated by exogenous taurine, hypotaurine, -alanine and GABA, whereas GABA, nipecotic acid and homotaurine effectively enhanced GABA release. The stimulatory potency of the analogues closely corresponded to their ability to inhibit taurine and GABA uptake, respectively, indicating that these efflux processes could be mediated by the carriers operating outwards. Glutamate induced GABA release, whereas taurine efflux was potentiated by aspartate, glutamate, cysteate, homocysteate and kainate. The centrally acting drugs, including GABA agonists and antagonists, as well as the proposed taurine antagonist TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide), had no marked effects on spontaneous taurine and GABA release. Potassium ions stimulated dosedependently both taurine and GABA release from the slices, the responses of taurine being strikingly slow but sustained. Exogenous GABA and nipecotic acid accelerated the potassium-stimulated GABA release, whereas picrotoxin and bicuculline were ineffective. The potassium-stimulated taurine release was unaltered or suppressed by exogenous taurine and analogues, differing in this respect from GABA release. The apparent magnitude of the depolarization-induced GABA release is thus influenced by the function of membrane transport sites, but the same conclusion cannot be drawn with regard to taurine. Haloperidol and imipramine were able to affect the evoked release of both taurine and GABA. 相似文献
4.
9-β-
-Arabinofuranosyl-2-fluoroadenine (F-ara-A) and 9-β-
-arabinofuranosyladenine (ara-A) are purine nucleoside analogues which are incorporated into nucleic acids. This study demonstrates the mutagenic properties of F-ara-A and ara-A and provides evidence for mechanisms by which the arabinosyl nucleosides induce mutation. At the drug dosages that evoked exponential cell killing, F-ara-A and ara-A caused a significant increase in the number of 6-thioguanine-resistant mutants in Chinese hamster ovary cells. Southern analyses showed that 15 of 16 drug-induced mutants had lost all or part of the HPRT gene, whereas no loss of the gene was found in 4 spontaneous mutants. We conclude that both F-ara-A and ara-A induced mutation predominantly by causing deletion of genetic method. The remarkable frequency of gene deletion among these drug-induced mutations is discussed with respect to possible mechanisms of action of arabinosyl nucleosides in mutational studies. 相似文献
5.
A. Benayad D. Benamar N. Van Mau G. Page F. Heitz 《European biophysics journal : EBJ》1991,20(4):209-213
Three different gramicidin A analogues bearing acyl chains of various length on the ethanolamine moiety have been studied by investigating their single channel behaviour and their monolayer properties. It is shown that the single channel conductance does not depend on the substitution of the ethanolamine OH group and that the channel lifetime is roughly proportional to the length of the alkyl chain. The monolayer study indicates that acylation of gramicidin A produces compounds which have medium-dependent conformations. These acylated compounds are miscible with lipids, while GA is not, and the surface potential is not modified by the esterification of the alcohol group.
Offprint requests to: F. Heitz 相似文献
6.
Ralf Schmidt Klaus Neubert Alfred Barth Claus Liebmann Martin Schnittler Nga N. Chung Peter W. Schiller 《Peptides》1991,12(6):1175-1180
Cyclic analogues of the β-casein-derived opioid peptide β-casomorphin-5 (H-Tyr-Pro-Phe-Pro-Gly-OH) were prepared through substitution of the Pro2 residue with various ,ω-diamino acid residues (lysine, ornithine, 2,4-diaminobutyric acid) and cyclization of the ω-amino group to the C-terminal carboxyl function. Compounds of this type, with D-configuration at the 2-position residue, showed high opioid receptor affinity with some preference for μ receptors over δ receptors, high potency in the guinea pig ileum assay and considerable activity in the mouse vas deferens assay. Configurational inversion at the 4-position in these cyclic analogues resulted in enhanced affinity for both μ and δ receptors, whereas N-methylation of the Phe3 residue produced a potency decrease. 相似文献
7.
Distamycin and netropsin are two oligopeptides which bind to DNA in a nonintercalative manner. Analogues of distamycin have
been synthesized and their binding with poly d(A-T) studied using ultraviolet absorption spectroscopy. Preliminary biological
activity tests on a gram positive bacteria using these analogues have also been carried out
Based on the lecture given by Dr. V. Sasisekharan at the Royal Society of Chemistry (Deccan Section) Bangalore, 26 June 1984. 相似文献
8.
Biochemical significance of enhanced activity of fluorinated 1,25-dihydroxyvitamin D3 in human cultured cell lines 总被引:1,自引:0,他引:1
Several human cancer cells possess receptors for 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]. In these cells 1,25-(OH)2D3 has a biphasic concentration-dependent regulatory effect on cell replication and specifically induces its own metabolism. We have studied the effects on these parameters of the native hormone together with those of two analogues fluorinated at the 24-carbon and of 1,24R,25-trihydroxyvitamin D3[1,24R,25-(OH)3D3]. The difluorinated analogue 24,24-difluoro-1,25-(OH)2D3[24,24-F2-1,25-(OH)2D3] is an approximately fivefold more potent inhibitor of cellular replication than the native hormone, while 1,24R,25-(OH)3D3 is about fivefold less potent. This enhanced potency of the fluorinated analogue parallels its enhanced potency in in vivo studies of its effects on calcium and mineral metabolism. However, although the analogue retains replication stimulatory activity, it is clearly no more potent than the native hormone in this activity: 1,24R,25-(OH)3D3 has no significant stimulatory activity. Exposure of the cells to 1,25-(OH)2D3 at 0.05 nM for 6 h increases the subsequent conversion of labelled hormone to aqueous phase soluble compounds by 6.7-fold. None of the other compounds had a similar effect at this concentration. At 10 nM all 1-hydroxylated compounds increased aqueous phase radioactivity about equally (13 to 17-fold); this effect is still specific since 25-OH D3 had no such effect even at 10 nM. Studies on the effects of the fluorinated analogues upon receptor binding of hormone in cell cytosols and uptake of hormone by intact cells clearly demonstrate that the enhanced activity of these analogues is not due to higher receptor affinity or more rapid access to intracellular receptor.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
[3H]Glutamate uptake into astrocytes in primary culture was potently inhibited by the aspartate analoguesl- andd-aspartic acid,Dl-threo--hydroxy-aspartic acid,l-aspartic acid--hydroxymate (IC50's: 136, 259, 168, and 560 M, respectively) and by -Dl-methylene-aspartate, a suicide inhibitor of asparate aminotransferase (IC50: 524 M), and by the endogenous sulphur-containing amino acidl-cysteinesulfinic acid (IC50: 114 M). [3H]Glutamate uptake was not significantly affected by either N-methyl-d-aspartate orDl-homocysteine thiolactone. These results demonstrate that other excitatory amino acids including aspartate andl-cysteinesulfinic acid (but excludingl-homocysteic acid) interact with the glutamate transport system of astrocytes. Inhibition of glutamate uptake may significantly increase the level of neuronal excitability. 相似文献
10.
Abstract: Somatostatin (SS) is a neuropeptide that is distributed in various regions of the CNS, where it may act as a neurotransmitter or neuromodulator. SS produces multiple effects in the CNS through interactions with membrane receptors. In particular, SS inhibits various secretory responses in different cell types. In the present study, we have investigated the effects of exogenous application of SS on the intracellular free Ca2+ concentration ([Ca2+ ]i ) in PC12 cells, a rat pheochromocytoma cell line. SS did reduce the magnitude of the secondary, maintained Ca2+ influx brought about by K+ depolarization. Similar effects were obtained with the application of SS analogues, such as d -Trp8 -SS, d -Trp8 - d -Cys14 -SS, CGP-23996, and SMS-201995. In addition, treatment with cyclo-SS, a SS antagonist, did not alter [Ca2+ ]i . Experiments with selective blockers of different voltage-dependent Ca2+ channels, such as methoxyverapamil (D600) and Ω-conotoxin GVIA, demonstrated that the effects of SS on [Ca2+ ]i were mediated by voltage-dependent Ca2+ channels of the L type. Control experiments with a membrane potential indicator, i.e., the fluorescent dye bisoxonol, excluded that SS influenced the level of the membrane potential. SS effects on PC12 cells suggest the possibility that this neuropeptide plays a role in the modulation of cell functional activity by altering Ca2+ influx. 相似文献