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Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca2+ store depletion these SOCs could also be activated by α-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of β-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective β-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl- sn -glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of β-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation. 相似文献
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The antimutagenic effect of ethanolic extract of propolis (EEP) and honeybee (Apis mellifera) venom, both collected in the State of S?o Paulo, Brazil, was assessed by the Salmonella/microsome assay upon direct- and indirect-acting mutagens. EEP had inhibitory effect (in an ascending order) on the mutagenicity power of daunomycin (TA102), benzo(a)pyrene (TA100), and aflatoxin B(1)(TA98) and the venom acted against the mutagenicity of 4-nitro-o-phenylenediamine (TA98) and daunomycin (TA102). Teratogenesis Carcinog. Mutagen. 19:403-413, 1999. 相似文献
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The primary structure of TsTX-IV, a neurotoxin isolated from Tityrus serrulatus scorpion venom, is reported. Its amino acid sequence was determined by automated Edman sequential degradation of the reduced and carboxymethylated toxin and of relevant peptides obtained by digestion with Staphylococcus aureus strain V8 protease or trypsin and cleavage by CNBr. The complete sequence showed 41 amino acid residues, which account for an estimated molecular weight of 4520, and eight half-cystine residues which cross-link the toxin molecule with four disulfide bonds. The molecular weight determined by mass spectrometry was 4518. Comparison of this sequence with those from other scorpion toxins showed a resemblance with toxins which act on different types of K+ channels. TsTx-IV was able to block Ca2+-activated K+ channels of high conductance. TsTX-IV is the first four-disulfide-bridged short toxin from T. serrulatus so far completely sequenced. 相似文献
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目的:观察应用凌晨3:00皮下注射短效胰岛素治疗2型糖尿病黎明现象的疗效。方法:对40例有黎明现象的2型糖尿病患者,使用短效胰岛素凌晨3:00注射4~6U。抽取肘静脉血测定空腹血糖(FPG)及早餐后2h血糖(2hPG),免疫比浊法测定糖化血红蛋白(HbA1c),比较治疗前后上述指标变化。结果:本组患者FPG从治疗前(9.5±1.6)mmol/L下降至(6.0±0.4)mmol/L,治疗2个月后仍保持为(5.6±0.4)mmol/L;2hPG从治疗前(13.8±0.8)mmol/L下降至(7.4±0.4)mmol/L,在治疗2个月后保持为(7.9±0.3)mmol/L;FPG和2hPG与治疗前比较,均具有显著性差异(P<0.01)。治疗2个月后,HbA1c从治疗前(8.3±0.6)%下降至(6.5±0.3)%,与治疗前比较,有显著性差异(P<0.01)。结论:短效胰岛素强化治疗黎明现象具有快速稳定的降血糖和降糖化血红蛋白作用。 相似文献