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381.
Stimulus-secretion coupling in exocrine glands involves Ca2+ release from intracellular stores. In endoplasmic reticulum vesicle preparations from rat exocrine pancreas, an inositol 1,4,5-trisphosphate(InsP3)-sensitive, as well as an InsP3-insensitive, Ca2+ pool has been characterized. But Ca2+ channels in the endoplasmic reticulum of rat exocrine pancreas have not been demonstrated at the level of single-channel current. We have now used the patch-clamp technique on endoplasmic reticulum vesicles fused by means of the dehydration-rehydration method. In excised patches, single Ba2(+)- and Ca2(+)-selective channels were recorded. The channel activity was markedly voltage-dependent. Caffeine increased channel open-state probability, whereas ruthenium red and Cd2+ blocked single-channel currents. Ryanodine, nifedipine and heparin had no effect on channel activity. The channel activity was not dependent on the free Ca2+ concentration, the presence of InsP3, or pH. We conclude that this calcium channel mediates Ca2+ release from an intracellular store through an InsP3-insensitive mechanism. 相似文献
382.
Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. 总被引:46,自引:0,他引:46
Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects. 相似文献
383.
Expression and characterization of the cystic fibrosis transmembrane conductance regulator. 总被引:36,自引:0,他引:36
R J Gregory S H Cheng D P Rich J Marshall S Paul K Hehir L Ostedgaard K W Klinger M J Welsh A E Smith 《Nature》1990,347(6291):382-386
Cystic fibrosis (CF) is a common lethal genetic disease that manifests itself in airway and other epithelial cells as defective chloride ion absorption and secretion, resulting at least in part from a defect in a cyclic AMP-regulated, outwardly-rectifying Cl- channel in the apical surface. The gene responsible for CF has been identified and predicted to encode a membrane protein termed the CF transmembrane conductance regulator (CFTR). Identification of a cryptic bacterial promoter within the CFTR coding sequence led us to construct a complementary DNA in a low-copy-number plasmid, thereby avoiding the deleterious effects of CFTR expression on Escherischia coli. We have used this cDNA to express CFTR in vitro and in vivo. Here we demonstrate that CFTR is a membrane-associated glycoprotein that can be phosporylated in vitro by cAMP-dependent protein kinase. Polyclonal and monoclonal antibodies directed against distinct domains of the protein immunoprecipitated recombinant CFTR as well as the endogenous CFTR in nonrecombinant T84 cells. Partial proteolysis fingerprinting showed that the recombinant and non-recombinant proteins are indistinguishable. These data, which establish several characteristics of the protein responsible for CF, will now enable CFTR function to be studied and will provide a basis for diagnosis and therapy. 相似文献
384.
385.
Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins 总被引:59,自引:0,他引:59
A complementary DNA encoding the D100 polypeptide of rat brain dynamin--a force-producing, microtubule-activated nucleotide triphosphatase--has been cloned and sequenced. The predicted amino acid sequence includes a guanine nucleotide-binding domain that is homologous with those of a family of antiviral factors, inducible by interferon and known as Mx proteins, and with the product of the essential yeast vacuolar protein sorting gene VPS1. These relationships imply the existence of a new family of GTPases with physiological roles that may include microtubule-based motility and protein sorting. 相似文献
386.
387.
本文将文献[3]的引理1推广到s-单式环上,并用迭代技术给出文献[4]的定理2一个简易的证明,将若干有1环的交换性定理推广到s-单式环上。 相似文献
388.
探讨了溅射用铁电陶瓷靶(PZT,PLZT)的烧结工艺,并对其显微结构进行了分析。结果表明,采用新的烧结工艺(含保护措施),可以有效地抑制PbO的挥发,制备出组织结构及成分均匀、PbO含量正常、致密度较高、不变形的符合磁控溅射要求的铁电陶瓷烧结靶。 相似文献
389.
强反射层追踪与相对时差拾取中的“多值”现象严重影响剩余静校正的效果,为此提出的小波包预处理方法,可以实现地震道噪声与信号及不同强反射层的分离,从而能自动识别并提取“纯”的强反射层,提高强反射层追踪的可靠性和相对时差的拾取精度. 相似文献
390.
对几种逆变电源的抗冲击性负荷电路进行分析,给出了一种便于实现且效果很好的电路,实验证明此电路对各种冲击负荷甚至输出短路都能进行很好的限流,可以彻底解决逆变电源在负载冲击下频繁停机的问题。 相似文献