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61.
Pseudo-peptide bond inhibitors (-bond inhibitors) and peptide-aldehyde inhibitors of atrial granule serine proteinase, the candidate processing enzyme of pro-atrial natrieuretic factor, are prepared in high yield and purity by novel synthetic routes. The -bond compounds retain essential residues for enzyme binding, but place the enzyme inhibition site in the midst of the peptide sequence. Thus, Bz-APR--LR and Bz-APR--SLRR can be considered readthrough inhibitors of atrial granule serine proteinase. The most potent -peptide, Bz-APR--SLRR (IC50=250 M), is about fivefold less potent than the best peptide-aldehyde inhibitor (EACA-APR-CHO), and both the -bond and peptide-aldehyde compounds are competitive, reversible inhibitors of the enzyme. The -bond peptides containing two C-terminal Arg residues are three-to tenfold more potent than the analogous compounds containing only one C-terminal Arg residue, confirming the importance of both Arg residues in the enzyme processing recognition site. As expected, because of their moderate potencies, the -peptides are not useful affinity ligands for purification of atrial granule serine proteinase, but both peptide aldehydes are effective affinity ligands [Damodaran and Harris (1995),J. Protein Chem., this issue].Abbreviations AGSP
atrial granule serine proteinase
- ANF
atrial natriuretic factor
- Bz
benzoyl
- DIEA
diisopropylethylamine
- DIPCDI
diisopropylcarbodiimide
- DMF
dimethylformamide
- DMSO
dimethylsulfoxide
- EACA
6(e)-aminocaproic acid
- EtOAc
ethyl acetate
- HEPES
N-2-hydroxyethylpiperazine-N-propanesulfonic acid
- HOBt
N-hydroxybenzotriazole
- HPLC
high-performance liquid chrornatography
- NMR
nuclear magnetic resonance
- PEG
polyethylene glycol-3350
- PyBOP
benzotriazole-1-yl-oxy-trispyrrolidino-phosphonium-hexafluorophospate
- TEA
triethylamine
- TFA
trifluoroacetic acid
- THF
tetrahydrofuran
- TLC
thin-layer chromatography
- UV
ultraviolet
-
pseudo-peptide bond -CH2-NH-. Single-letter abbreviations are used to denote amino acids 相似文献
62.
本文报道大鼠水盐负荷时,其心房特殊颗粒(ASG)的数目及钙含量发生相关变化。给大鼠禁水5d或饮2%NaCl液4d造成水盐负荷,用电镜形态计量法计数ASG,以反映心房钠尿肽(ANP)的分泌水平,电镜X射线显微分析法测定ASG中钙、硫含量及肌质同终末池(TSR)中钙含量。结果显示,禁水引起ANP分泌减少时,ASG的数密度增加(6.02±2.30增至9.97±3.21个/μm3),同时伴有钙含量增加(64±16增至92±18mmol/kg);饮盐水引起ANP分泌增加时,ASG的数密度减少(6.02±2.30减至2.96±1.62个/μm3),巨伴有钙含量减少(64±16减至38±22mmol/kg),但水盐负荷对TSR中钙浓度无任何影响。据此推论ASG作为细胞内钙库,借某种机制调控其中钙的释放而参与ANP的刺激分泌耦联过程。 相似文献
63.
心房钠尿因子对麻醉家兔局部血流的影响 总被引:3,自引:2,他引:1
在42只麻醉家兔,观察了静脉注射心房肽Ⅱ(AtriopeptinⅡ,APⅡ)对局部血流量以及动脉内注射 AP Ⅱ 对局部血管阻力的影响。结果如下:(1)静脉注射 APⅡ(30μg/kg)5min后,平均动脉压(MAP)降低11.0±1.5mmHg(n=8,M±SE,下同),与溶剂对照组相比有明显差异(P相似文献
64.
Cyclic stretch induces the release of growth promoting factors from cultured neonatal cardiomyocytes and cardiac fibroblasts 总被引:9,自引:0,他引:9
Ruwhof C van Wamel AE Egas JM van der Laarse A 《Molecular and cellular biochemistry》2000,208(1-2):89-98
Growth factors and hormones may play an autocrine/paracrine role in mechanical stress-induced cardiac hypertrophy. Using an in vitro model of mechanical stress, i.e. stretch of cardiomyocytes and cardiac fibroblasts, we tested the involvement of growth factors and hormones in this process.We found that conditioned medium (CM) derived from 4 h cyclicly (1 Hz) stretched cardiomyocytes increased the rate of protein synthesis in static cardiomyocytes by 8 ± 3%. Moreover, CM derived from 2 h stretched fibroblasts increased the rate of protein synthesis in static fibroblasts as well as in static cardiomyocytes by 8 ± 2 and 6 ± 2%, respectively. Analysis of CM using size-exclusion HPLC showed that cardiomyocytes and fibroblasts released at least three factors with MW 10 kD, their quantities being time-dependently increased by stretch. Subsequent analyses using immunoassays revealed that cardiomyocytes released atrial natriuretic peptide (ANP) and transforming growth factor-beta1 (TGF1) being increased by 45 ± 17 and 21 ± 4% upon 4 h of stretch, respectively. Fibroblasts released TGF1 and very low quantity of endothelin-1 (ET-1). The release of TGF1 was significantly increased by 18 ± 4% after 24 h of stretch in fibroblasts. Both cell types released no detectable amount of angiotensin II (Ang II).In conclusion, upon cyclic stretch cardiomyocytes and fibroblasts secrete growth factors and hormones which induce growth responses in cardiomyocytes and fibroblasts in an autocrine/paracrine way. TGF secreted by cardiomyocytes and fibroblasts, and ANP secreted by cardiomyocytes are likely candidates. We found no evidence for the involvement of Ang II and ET-1 in autocrine/paracrine mechanisms between cardiac cell types. 相似文献
65.
66.
培养的卒中型自发性高血压大鼠(SHR_(sp))及其对照 WKY 大鼠主动脉平滑肌细胞(VSMC)上存在心房钠尿肽(ANP)的特异性受体,它们与~(125)I-ANP 的最大结合量(B_(max))是:SHR_(sp)3.65±0.13和 WKY 1.89±0.09 pmol/mg pr(P<0.01);解离平衡常数(Kd)值分别是72.6±10.2和42.0±4.8×10~(-12)mol/L(P<0.01)。 两种细胞内介导舒血管作用的第二信使、环磷酸乌苷(cGMP)的基础浓度无显著差异,对相同剂量 ANP 刺激引起 cGMP 分别增加139(SHRsp)和271(WKY)倍。可见 SHRsp 的 VSMC ANP 受体数量虽比 WKY大鼠增多,但对相同剂量 ANP 引起的 cGMP 增加反应及 ANP 受体的亲和力均显著降低。高盐培养液孵育24h 后,细胞表面 ANP 受体的亲和力改变不明显,但受体数量下调,SHRsp 和 WKY 大鼠分别降至对照的34.8±8.2%和38.6±9.4%,细胞对 ANP 引起的 cGMP增加反应明显降低,且均以 SHR_(sp)较显著。提示后两种变化可能在高盐促进血压升高的机制中起作用。 相似文献
67.
给完整的及切除肾上腺的雌性 Wistar 大鼠分別注射地塞米松、去氧皮质酮或地塞米松加去氧皮质酮;冷酚法提取心房总 RNA,用α-~(32P)标记的大鼠心房肽 cDNA 探针与之杂交。完整大鼠接受地塞米松和切除肾上腺后接受地塞米松加去氧皮质酮的大鼠,心房肽基因转录产物增加2倍,其余组无显著变化。结果提示糖皮质激素可促进心房肽基因表达,但此作用依赖于盐皮质激素的同时存在,单纯盐皮质激素不能增强该基因的表达。 相似文献
68.
69.
70.
目的:为研究钙离子对人心房肌细胞小电导钙激活钾通道电流(ISK2)的调节作用,建立用二性霉素B(amphotericin B)与β-escin穿孔的膜片钳(PPR)技术。方法:体外循环术中取得右心耳,应用急性酶分离获得单个人体心房肌细胞,用二性霉素B和/或β-escin作为穿孔电极液,进行穿孔膜片钳实验,在此模式下测试钙离子对人心房肌细胞SK2电流的调控作用,并用胞内钙测试系统验证穿孔前后胞内钙变化。结果:混合使用穿孔电极液6.88μg/mlβ-escin和150μg/ml二性霉素B与单独用150μg/ml二性霉素B或6.88μg/mlβ-escin相比,前一种方法细胞容易封接,能形成稳定的穿孔膜片钳记录模式,可观察到SK2电流有激活,且胞内钙测试系统检测时可观察到穿孔后电极液至细胞内的游离钙离子浓度的增加,F340/380增强。结论:适当浓度的二性霉素B与β-escin混合使用进行穿孔膜片钳实验是一种稳定的全细胞膜片的记录技术,可以用于胞内游离钙离子对SK2电流调控的研究。 相似文献