降钙素基因相关肽对犬冠脉流量及冠状动脉的作用

本研究通过整体及离体灌流实验观察到重庆冠脉狭窄时，犬冠脉流量（ＣＢＦ），平均动脉压（ＭＡＰ）明显减小，而心率（ＨＲ）则增加。狭窄３０ｍｉｎ后由冠状动脉注射降钙素基因相关肽（ＣＧＲＰ）０．３μｇ／ｋｇ后，ＣＢＦ、ＭＡＰ和ＨＲ可恢复正常水平。同时，缺血犬的离体冠状动脉对ＣＧＲＰ的反应也出现改变。大冠脉舒张反应明显降低，而小冠脉的舒张反应与正常相比，无明显改变，这可能与缺血后大冠脉的内皮细胞容易损伤有关。同时也提示:急性心肌缺血时，冠脉流量的减少，主要由于小冠状动脉收缩所致。     

A VIP antagonist distinguishes VIP receptors on spinal cord cells and lymphocytes

Vasoactive intestinal peptide (VIP) is a neuropeptide which also interacts with cells of the immune system. The paucity of specific VIP receptor antagonists has hampered studies of possible receptor heterogeneity and of VIP function. To aid in achieving these goals, a new VIP antagonist, a hybrid between neurotensin and VIP, has been synthesized. This peptide interacted with VIP receptors on spinal cord cells with an affinity 10-fold greater than VIP itself. In contrast, 1000-fold higher concentrations of the antagonist were required to displace labeled VIP from its receptor on lymphoid cells as compared to VIP itself, suggesting VIP receptor heterogeneity between immune and spinal cord cells.     

急性等容性血液稀释对血浆ET和CGRP水平的影响

目的　探讨急性等容性血液稀释 (ANH)对血浆内皮素 (ET)和降钙基因相关肽(CGRP)水平的影响。方法　选择非心脏手术ASAⅠ～Ⅱ级患者 2 0例 ,麻醉前快速输入复方乳酸钠1 0～ 1 5ml/kg。麻醉后从桡动脉放血 1 0ml/kg ,同时经静脉输入等量的 4 %琥珀酰明胶。观察ANH麻醉前 (T0 )、血液稀释完成后 1 0min(T1 )、2 0min(T2 )、30min(T3 )的血液动力学、血浆ET和CGRP浓度的变化。结果　ANH前后MAP、HR、SpO2 和ECG均较稳定。ANH后 1 0min、2 0min血浆ET水平分别为 (1 4 4 4 7± 1 9 1 7) pg/ml和 (1 5 7 1 7± 1 2 4 5 ) pg/ml,但明显高于ANH前的 (1 2 7 6 8±2 0 92 ) pg/ml(P <0 0 5 )。ANH后 1 0min、2 0min血浆CGRP水平分别为 (5 4 72± 2 5 6 5 )pg/ml和(5 5 32± 1 7 94 )pg/ml,也明显高于ANH前的 (4 4 6 2± 1 6 90 ) pg/ml(P <0 0 5 )。而ET/CGRP比值无明显变化。结论　ANH近期血浆ET和CGRP水平均有一定的增加 ,但ET/CGRP比值的变化无统计学意义 ,同时心血管反应不明显 ,表明血浆ET和CGRP的动态平衡对ANH时的循环稳定起着重要的作用     

CGRP免疫反应神经纤维在大鼠胆总管与十二指肠连接处的分布

用免疫组织化学ＡＢＣ法，研究了降钙素基因相关肽（ＣＧＲＰ）免疫反应神经纤维在大鼠胆总管末端与十二指肠连接处的分布。大鼠的胆总管末端有较丰富的ＣＧＲＰ免疫反应神经纤维，它们多呈串珠（膨体）状，少数为无膨体的细长纤维。ＣＧＲＰ－ＩＲ纤维主要分布肌层及血管周围，在神经纤维的附近可见到含ＣＧＲＰ－ＩＲ阳性颗粒的肥大细胞。本实验为神经免疫调节机制的研究提供了形态学依据。     

ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS AND KININ METABOLISM: EVIDENCE THAT ACE INHIBITORS MAY INHIBIT A KININASE OTHER THAN ACE

1. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, and also metabolizes bradykinin-(1–9) to bradykinin-(1–7) and bradykinin-(1–7) to bradykinin-(1–5). Increases in endogenous kinin levels may contribute to the therapeutic effects of ACE inhibitors. 2. ACE inhibitors increase vascular levels of both bradykinin-(1–9) and its ACE cleavage product bradykinin-(1–7), at doses below the threshold for ACE inhibition, leading to the proposal that ACE inhibitors may also inhibit a non-ACE kininase which cleaves both kinin peptides; this non-ACE kininase may be the major pathway of kinin metabolism in the vasculature and some other tissues. 3. In support of this proposal, ACE inhibitors potentiate bradykinin-(1–9) effects at doses which have little or no effect on ACE activity, as indicated by angiotensin I conversion to angiotensin II. ACE inhibitors also potentiate the actions of ACE-resistant kinin analogues, which may be susceptible to metabolism by a non-ACE kininase. 4. Identification and characterization of the putative non-ACE kininase which is inhibited by ACE inhibitors may reveal novel approaches to the tissue-specific modulation of kinin levels.     

SD大鼠肺中降钙素基因相关肽的分布及缺氧对其含量的影响

本研究用免疫细胞化学方法(ABC法)观察了降钙素基因相关肽(CGRP)在SD大鼠肺中的分布,缺氧对肺中神经内分泌细胞内CGRP含餐的影响。结果表明:含CGRP的神经纤维分布在肺血管平滑肌层中及其周围、气管-支气管树的粘膜下层;含CGRP的神经内分泌细胞位于气管一支气管树的上皮层、粘液腺中和肺实质内。缺氧不引起火鼠肺的神经内分泌细胞数目改变,但可使这些细胞内的CGRP含量增加。     

内皮素和降钙素基因相关肽与梗阻性黄疸大鼠门脉压力的关系

目的　通过测定梗阻性黄疸大鼠门静脉血中内皮素和降钙素基因相关肽浓度 ,探讨内皮素和降钙素基因相关肽在梗阻性黄疸鼠门脉压力升高中的作用。方法　建立大鼠梗阻性黄疸模型 ,采用放射免疫法测定门静脉血中内皮素和降钙素基因相关肽的浓度。结果　内皮素在胆道结扎后各时相均明显升高 (P<0 .0 5 ) ,3天达峰值 (186.99± 3 6.0 3 pg/ m l) ,降钙素基因相关肽在胆道结扎后第 1天无明显变化 (2 13 .11± 3 5 .3 8pg/ m l vs 180 .14± 3 0 .66pg/ ml) ,3天后明显升高 ,并与对照组相差明显 (P<0 .0 5 )。梗阻性黄疸组大鼠门脉压力在各时相组均比对照组明显升高 (P<0 .0 5 )但未形成门脉高压。内皮素抗血清治疗可降低内皮素浓度和升高的门静脉压力。结论　梗阻性黄疸时内皮素和降钙素基因相关肽浓度均升高 ,失去内皮素和降钙素基因相关肽的正常平衡并伴有门脉压力的升高     

Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy

In order to investigate the validity of the hypothesis that acid-soluble peptides (ASP) in urinary excreta can be applied as an index of the protein catabolism of the whole body, we measured the urinary excretion of ASP in 46 normal children and in 18 children with Duchenne muscular dystrophy (DMD), in which continuous breakdown of skeletal muscle protein is presumed. The mean value of ASP in the children with DMD was significantly higher than that in normal controls. The concentration of ASP was correlated with that of 3-methylhistidine (3MH), which has been proposed as an index of muscle breakdown. This finding indicates that urinary ASP reflects the catabolism of body proteins. No correlation was observed between the concentration of ASP and that of 1-methylhistidine (1MH), which is used as an objective index of meat and fish ingestion. After the administration of bestatin, an inhibitor of leucine aminopeptidase, for 9 months, the urinary ASP concentration of children with DMD increased markedly. This increase is thought to have been directly caused by the bestatin itself. Urinary ASP is therefore apparently a more conveniently applied index of protein catabolism than is urinary 3MH, which requires the application of several restrictions. However, it should not be applied when the effect of bestatin administration is evident.     

Interaction of glucagon with artificial lipid bilayer membranes

The enhancement of fluorescence emission from the tryptophan residue of glucagon, the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl stearic acid, circular dichroism spectra, the release of 6-carboxytluorescein, and polarized infrared attenuated total reflection (IR-ATR) spectra were used to study the interaction of glucagon with intact lipid vesicles and flat bilayers. Dimyristoylphosphatidylcholine bound the peptide only below the main transition temperature, thus confirming earlier results of Epand et al. (1977). However, the peptide is also bound by vesicles of unsaturated lipids above their transition temperature, suggesting an influence of lipid area on the binding process. Circular dichroism showed that binding to such vesicles also increases the helix content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(I-13)-tridecapeptide revealed profound differences in orientation of the two peptides. The dichroic ratios and the derived order parameters indicated an isotropic orientation of the helical segments of glucagon, but did not exclude a principal orientation of the molecules lying flat on the nienibrane surface. In contrast, the axis of the dynorphin helix is clearly oriented normal to the interface. The two peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a deeper penetration of the primary amphiphilic helix of dynorphin A-(I-13) than of the secondary amphiphilic helix of glucagon.     

Continuous flow synthesis of peptides using a polyacrylamide gel resin (Expansin™)

The continuous flow syntheses of endothelin 1, proendothelin 2. ATP binding site of the CDC2 kinase 3, and fragment 18-30 of an actin 4, have been performed by using a polyacrylamide gel resin Expansin? (about 0.6 mmol NH₂/g) with the glycolamidic ester handle as labile anchorage. In addition, we report here a method of air oxidation which reduces the formation of side-products related to the formation of intermolecular disulfide bridges.