Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5u/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on S-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC₅₀, 0.02 μM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC₅₀,0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E₃ and 10 E₅) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.     

The pro-LHRH system of the rat brain. effects of changes in the endocrine background

The gonadotropin-releasing hormone-associated peptide (GAP) and luteinizing hormone-releasing hormone (LHRH) portions of the LHRH precursor were localized by immunocytochemistry in prepubertal female rats, in adult female rats at different stages of the estrous cycle, and in ovariectomized rats. Our results indicate that GAP is present in the same population of neurons as LHRH in the rat brain. These results confirm the specificity of previous immunocytochemical studies which used antisera to LHRH alone. The endocrine status of the animal was demonstrated to affect the immunocytochemical appearance of the GAP system. The number of GAP immunopositive cells and terminals is highest during diestrus II and lowest on the day of estrus, suggesting either a role in and/or a dependence upon the endocrine changes associated with the estrous cycle. Ovariectomy results in a gradual decrease in GAP immunoreactivity in the median eminence. This observation, in concert with other recent studies, suggests that ovarian factors may be acting to maintain the LHRH system and that ovariectomy may result in decreased synthesis and/or processing of the LHRH system and that ovariectomy may result in decreased synthesis and/or processing of the LHRH precursor.     

36例慢牲肾功能不全患者血浆心钠素水平的观察

报告３６例慢性肾功能不全患者的血浆心钠素、肾素、血管紧张素Ⅱ、醛固酮水平及其相互关系。结果表明：①慢性肾功能不全患者的血浆心钠素水平明显高于对照组值（Ｐ＜０．０ｌ）；②慢性肾功能不全患者中并发高血压者与血压正常者血浆心钠素水平相近，但均高于对照组（Ｐ＜０．０１）；③慢性肾功能不全患者肾素—血管紧张素—醛固酮系统（ＲＡＡＳ）活性增高，但心钠素与醛固酮无明显相关。提示血浆心钠素测定在慢性肾功能不全的诊断中有重要意义。     

Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with β-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.     

Atrial natriuretic peptide and verapamil can prevent gentamicin induced acute renal failure in the rat

Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination.     

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。