垂体中叶素与心血管疾病相关性研究进展

垂体中叶素属于降钙素/降钙素基因相关肽家族,相对于家族成员其结构独特,具有调节心血管功能的多重效应,如扩张冠脉血管、影响血供、加强心肌收缩力、增加肾血流、对心血管疾病有抗损伤保护的作用等。本文将对其在心血管系统中的作用及研究进展进行综述。     

血管活性肽与微循环

心 血管系统合成和分泌多种小分子的生物活性物质 ,如血管活性多肽、生物活性氨基酸、细胞因子、生长因子和一氧化氮、一氧化碳、硫化氢等气体信号分子。这些生物活性分子具有分子量小、种类繁多、分布广泛、调节灵活和生物作用复杂等特点 ,对循环系统功能进行复杂调节 ,以维持心血管稳态 ,在心血管疾病的发生和发展中具有重要意义。血管活性多肽如内皮素 (endothelin ,ET)、肾上腺髓质素 (adrenomedullin ,ADM )、降钙素基因相关肽 (calcitoningene relatedpeptides ,CGRP)、血管紧张素 (angiotensin ,Ang)、心钠素 (atrialnatriuretic…     

肾上腺髓质素与心血管病理性重构

肾上腺髓质素(adrenomedullin,AM)是1993年从人嗜铬细胞瘤中分离出的由52个氨基酸组成的舒血管肽,属于降钙素基因相关肽超家族。该物质广泛分布于全身各个系统,尤其是心血管系统,如血管平滑肌细胞、内皮细胞、心肌细胞和成纤维细胞均可合成和分泌AM。研究表明,AM以自分泌或旁分     

小腿穴位区细胞外钙离子对血管的作用

探讨细胞外Ｃａ＾２＋对穴位区血管的作用,为进一步研究穴位的物质基础及穴位钙的作用提供资料。方法：用不同浓度的钙离子溶液在体局部孵育大鼠胫前动脉,光镜下观测免疫组化染色的血管周降钙素基因相关肽、神经肽Ｙ阳性神经纤维的密度改变。结果：当细胞外Ｃａ＾２＋浓度为生理浓度的１０倍时,胫前动脉周降钙素基因相关肽、神经肽Ｙ阳性神经纤维的密度均有所下降,以降钙素基因相关肽阳性神经纤维表现最为显著。结论：适度细胞外高钙可促进血管周神经释放降钙素基因的相关肽等神经活性物质,进而调节血管的功能。     

充血性心力衰竭患者血浆内皮素和降钙素基因相关肽水平的临床观察

近年来发现内皮素(ET)和降钙素基因相关肽(CGRP)分别是体内最强的缩血管和舒血管生物活性多肽[1,2],在体内它们广泛分布于中枢、周围神经系统和心血管系统及某些器官组织;目前在充血性心力衰竭(CHF)方面的大多数研究仅局限在ET和CGRP单方面的研究,CHF患者体内ET和CGRP平衡状态研究报道不多,为此本文同期检测了40例CHF患者血浆ET和CGRP水平,以及ET/CGRP比值,报道如下.     

充血性心力衰竭患者血浆内皮素和降钙素基因相关肽水平的？…

近年来发现内皮素(ET)和降钙素基因相关肽(CGRP)分别是体内最强的缩血管和舒血管生物活性多肽[1,2],在体内它们广泛分布于中枢、周围神经系统和心血管系统及某些器官组织;目前在充血性心力衰竭(CHF)方面的大多数研究仅局限在ET和CGRP单方面的研究,CHF患者体内ET和CGRP平衡状态研究报道不多,为此本文同期检测了40例CHF患者血浆ET和CGRP水平,以及ET/CGRP比值,报道如下.     

降钙素基因相关肽与免疫调节

降钙素基因相关肽（ＣＧＲＰ）是由降钙素（ＣＴ）／ＣＧＲＰ基因复合体在神经系统中表达、具有强大的扩血管作用的生物活性多肽。在体内可直接与Ｔ，Ｂ细胞、巨噬细胞上的受体结合，或是通过间接作用于淋巴细胞、成纤维细胞等发挥其免疫调节功能。进一步研究ＣＧＲＰ与机体免疫调节的关系，可为探讨肿瘤、真菌感染和内毒素休克的诱因或发病机制提供有效途径。     

降钙素基因相关肽与心血管系

降钙素基因相关肽(calcitonin gene-related peptide,CGRP)是由一级感觉神经节细胞和甲状腺C细胞产生,由感觉神经纤维末梢和甲状腺C细胞分泌的一种含37个氨基酸的多肽,它广泛分布在神经组织和其它组织中。1983年,Rosenfeld应用DNA基因重组技术和分子生物学技术的研究时发现,由降钙素基因转录的RNA在神经组织内产生了mRNA,此mRNA编码了一种新肽,并将其分离出来的遂命名为降钙素基因相关肽。本文重点介绍CGRP与心血管系的关系。一、CGRP神经纤维在心脏和血管的分布含CGRP的神经纤维象其它的感觉神经肽一样,广泛分     

老年人血循环中CGRP与高血压病的关系

降钙素基因相关肽(CGRP)广泛分布于中枢和外周神经系统以及某些器官组织中,它是目前已知最强的舒血管物质之一,对各系统,特别是心血管系统有着重要的调节作用。我们用放射免疫法对48例高血压老年患者进行了CGRP的检测,探讨老年高血压与CGRP的关连及临床意义。 对象和方法     

日本猴椎旁交感神经节中含肽神经元的研究

本实验系应用荧光免疫组织化学的方法观察猴下位腰段椎旁交感神经节(L_(6-7))中神经肽Y,血管活性肠肽,降钙素基因相关肽,和P物质的存在、分布情况以及它们与酪氨酸羟化酶的共存关系。结果表明,大量细胞呈神经肽Y免疫反应阳性,它们在神经节周边分布更为密集。中等数量的血管活性肠肽阳性细胞和小量降钙素基因相关肽细胞散在于神经节内。在经含有Colchiciue的培养液离体孵育12h的标本上,可见中等数量的P物质免疫反应阳性细胞。根据抗酪氨酸羟化酶(TH)抗体的免疫染色结果,神经节内的神经元可分为TH~+和TH~-两群,前者占大多数。相邻切片免疫染色结果表明,几乎所有神经肽Y免疫阳性细胞同时含有TH,而所有血管活性肠肽免疫反应阳性细胞均呈酪氨酸羟化酶免疫反应阴性。神经肽Y与血管活性肠肽无共存关系。降钙素基因相关肽存在于部分血管活性肠肽免疫反应阳性细胞中,即属于VIP~+/TH~-组。从以上结果得出结论,在猴下位腰段椎旁交感神经节中,神经肽Y与血管活性肠肽分别存在于TH~+和TH~-两个细胞群。即神经肽Y存在于TH阳性神经元中,血管活性肠肽和降钙素基因相关肽则存在于TH阴性神经元中。     

CGRP-mediated cardiovascular effect of nitroglycerin

Organic nitrates, including nitroglycerin, produce vascular relaxation by releasing nitric oxide in vascular tissues near the plasma member of smooth muscle cells of veins and arteries. Calcitonin gene-related peptide (CGRP), a major transmitter in capsaicin-sensitive sensory nerves, is widely distributed in cardiovascular tissues and the release of CGRP is regulated by multiple autacoids including nitric oxide (NO). CGRP exerts complex cardiovascular effects including potent vasorelaxation and protective effects on myocytes and endothelial cells. Nitroglycerin activates sensory nerves fibres to release CGRP by generating NO and increasing cGMP level, and that the cardiovascular effects of nitroglycerin are partly mediated by endogenous CGRP.     

Calcitonin gene-related peptide inhibits early B cell development in vivo

Recent in vitro studies suggest that calcitonin gene-related peptide (CGRP) inhibits early B cell differentiation; however, there is no evidence in the intact animal for a role for CGRP in B cell development. Here, we show that in vivo treatment of mice with CGRP reduces the number of IL-7 responsive B cell progenitors in bone marrow. A single CGRP treatment reduces IL-7-responsive B cell progenitors by up to 40% for up to 72 h. The reduction is dose-dependent and can be blocked by a CGRP receptor antagonist, CGRP(8-37). CGRP in serum following injection is highly elevated at 30 min but returns to basal levels by 4 h, suggesting that a single injection of CGRP has long-lasting effects on B cell development. This report provides the first direct in vivo evidence that CGRP, a neuropeptide with multiple effects on mature lymphocytes, also plays a regulatory role in early B cell development in the bone marrow.     

Calcitonin gene-related peptide antagonism attenuates the haemodynamic and glycaemic responses to acute hypoxaemia in the late gestation sheep fetus

The fetal defence to acute hypoxaemia involves cardiovascular and metabolic responses, which include peripheral vasoconstriction and hyperglycaemia. Both these responses are mediated via neuroendocrine mechanisms, which require the stimulation of the sympathetic nervous system. In the adult, accumulating evidence supports a role for calcitonin gene-related peptide (CGRP) in the activation of sympathetic outflow. However, the role of CGRP in stimulated cardiovascular and metabolic functions before birth is completely unknown. This study tested the hypothesis that CGRP plays a role in the fetal cardiovascular and metabolic defence responses to acute hypoxaemia by affecting sympathetic outflow. Under anaesthesia, five sheep fetuses at 0.8 of gestation were surgically instrumented with catheters and a femoral arterial Transonic flow-probe. Five days later, fetuses were subjected to 0.5 h hypoxaemia during either i.v. saline or a selective CGRP antagonist in randomised order. Treatment started 30 min before hypoxaemia and ran continuously until the end of the challenge. Arterial samples were taken for blood gases, metabolic status and hormone analyses. CGRP antagonism did not alter basal arterial blood gas, metabolic, cardiovascular or endocrine status. During hypoxaemia, similar falls in P _a,O2 occurred in all fetuses. During saline infusion, hypoxaemia induced hypertension, bradycardia, femoral vasoconstriction, hyperglycaemia and an increase in haemoglobin, catecholamines and neuropeptide Y (NPY). In contrast, CGRP antagonism markedly diminished the femoral vasoconstrictor and glycaemic responses to hypoxaemia, and attenuated the increases in haemoglobin, catecholamines and NPY. Combined, these results strongly support the hypothesis that CGRP plays a role in the fetal cardiovascular and metabolic defence to hypoxaemia by affecting sympathetic outflow.     

大鼠肾上腺的NADPH,NPY,CGRP,SP,c—fos细胞化学特性

目的 探讨肾上腺内分泌组织和神经组织的双重组织学特性。方法 组织化学和免疫组织化学技术,在光学显微下观察ＮＡＤＰＨ、ＮＰＹ、ＣＧＲＰ、ＳＰ、ｃ－ｆｏｓ在大鼠肾上腺的分布。结果 肾上腺皮质分布有ＮＰＹ阳性神经细胞和神经纤维、ＣＧＲＰ阳性神经纤维;肾上腺髓质分布有ＮＡＤＰＨ－ｄ阳性神经细胞和神经纤维、ＣＧＲＰ阳性神经纤维、ＳＰ阳性神经纤维、ｃ－ｆｏｓ阳性神经细胞和神经纤维。肾上腺皮质球状带、网状带、束状带细胞均ＮＡＤＰＨ－ｄ阳性,髓质部分嗜铬细胞ＮＡＤＰＨ－ｄ阳性,部分嗜铬细胞ＮＰＹ阳性,部分嗜铬细胞ＣＧＲＰ阳性,部分嗜铬细胞ＳＰ阳性。结论 大鼠肾上腺接受广泛的非经典递质的神经支配,特别是肽能神经支配的肾上腺实质细胞及髓质嗜铬细胞,能分泌多种神经肽物质。提示肾上腺的内分泌活动不仅受到复杂的神经调节而且也受到自身的活     

Evidence for a physiological role of central calcitonin gene-related peptide (CGRP) receptors in the control of food intake in rats

In the present study, we investigated the role of central calcitonin gene-related peptide (CGRP) and amylin receptors in mediating the anorectic effects of CGRP and amylin in rats chronically cannulated in the lateral brain ventricle. Intracerebroventricular (ICV) injection of the CGRP and amylin receptor antagonist CGRP(8–37) failed to influence the anorectic effects of peripherally injected CGRP and amylin. CGRP(8–37) alone, however, increased food intake in food deprived rats when administered 2 h before food presentation. Under the same experimental conditions, the more specific amylin receptor antagonists amylin(8–37) or AC 187 did not affect food intake. We therefore conclude, that CGRP is a physiological regulator of food intake within the central nervous system, acting at central CGRP receptors. Peripheral receptors, however, are likely to mediate the anorectic effects of peripherally administered amylin and CGRP.     

降钙素基因相关肽在中枢神经系统的研究进展

降钙素基因相关肽 (calcitoningene -relatedpeptide,CGRP)是一种生物活性肽 ,广泛分布于中枢神经系统和周围神经系统以及某些非神经组织。在中枢神经分布的CGRP参与机体多种调节机制 ,尤其对感觉和运动的调节 ,在胚胎发育、再生、神经内分泌等也有较强的调节作用。本文就CGRP的结构、分布、共存及在中枢各部的相关研究进行综述     

Engineering ex vivo-expanded marrow stromal cells to secrete calcitonin gene-related peptide using adenoviral vector

Calcitonin gene-related peptide (CGRP) is a target for cardiovascular gene therapy. Marrow stromal cells (MSCs) hold promise for use in adult stem cell-based cell and gene therapy. To determine the feasibility of adenoviral-mediated CGRP gene transfer into ex vivo-expanded MSCs, rat MSCs were isolated, ex vivo expanded, and transduced with adenoviruses. Adprepro-CGRP and AdntlacZ, adenoviral vectors containing prepro-CGRP or nuclear-targeted beta-galactosidase reporter gene ntlacZ under the control of Rous sarcoma virus promoter, were used. In this study, it can be shown that transduction efficiency of adenoviral-mediated gene transfer into ex vivo-expanded MSCs is dose dependent, transgene expression persists for more than 21 days in culture, and adenoviral transduction does not alter the proliferation or viability of MSCs. Transduced MSCs retain multipotentiality and transgene expression after cell differentiation. The expression and secretion of CGRP by Adprepro- CGRP-transduced MSCs was confirmed by Western blot analysis and enzyme immunoassay. The secretion of CGRP by Adprepro-CGRP-transduced MSCs is dose dependent, and the transduced cells release as much as 9.5 +/- 0.4 pmol CGRP/1 x 10(6) cells/48 hours (mean +/- standard error of mean, n = 3) into culture medium at a multiplicity of infection of 300. Furthermore, culture supernatant from Adprepro-CGRP-transduced MSCs increases intracellular cyclic AMP levels in pulmonary artery smooth muscle cells in culture. These findings suggest that replication-deficient recombinant adenovirus can be used to gene engineer ex vivo-expanded MSCs and that high-level secretion of biologically active CGRP can be achieved, underscoring the clinical potential of using this novel adult stem cell-based cell and gene therapy strategy for the treatment of cardiovascular diseases.     

Transient receptor potential vanilloid 1 expression and function in splenic dendritic cells: a potential role in immune homeostasis

Neuro‐immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance, triggering calcium‐channel transient receptor potential vanilloid 1 (TRPV1) on sensory nerves induces the release of calcitonin‐gene‐related peptide (CGRP), a neuropeptide known to moderate dendritic cell activation and T helper cell type 1 polarization. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well‐documented ‘neural’ ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen‐presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown down‐regulation of activation markers CD80/86 on dendritic cells, and up‐regulation of interleukin‐6 and interleukin‐10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis.     

Expression of calcitonin gene-related peptide, adrenomedullin, and receptor modifying proteins in human adipose tissue and alteration in their expression with menopause status

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a vasoactive, proinflammatory neuropeptide implicated in the pathogenesis of cardiovascular disease. Elevated CGRP levels during hot flushes and pregnancy suggest that reproductive hormones may influence CGRP secretion. CGRP and the related protein adrenomedullin (ADM) may function through adipose tissue-mediated effects, since adipose tissue is an important site of cytokine production and the main site for estrogen production after menopause. This study examined mRNA and protein expression of CGRP, ADM, and the receptor activity-modifying proteins and the effects of menopausal status in human adipose tissue. DESIGN: Protein/mRNA levels were determined in adipose tissue biopsy samples collected from premenopausal (n = 22: follicle-stimulating hormone, <20 IU/L; estradiol [mean +/- SEM], 434.5 +/- 87.81 pmol/L) and postmenopausal (n = 25: follicle-stimulating hormone, >20 IU/L; estradiol, 43.4 +/- 6.95 pmol/L) women. RESULTS: Our studies determined that CGRP, ADM, and receptor activity-modifying proteins were expressed in abdominal fat, adipocytes, and preadipocytes. CGRP and ADM mRNA levels were increased in abdominal subcutaneous fat in postmenopausal women compared with premenopausal women (betaCGRP: premenopause Delta cycle threshold [Ct], 31.07 +/- 0.28 vs postmenopause DeltaCt, 30.35 +/- 0.17, P = 0.035; ADM: premenopause subcutaneous fat DeltaCt, 12.41 +/- 0.2 vs postmenopause subcutaneous fat DeltaCt, 11.55 +/- 0.14, P < 0.001) with CGRP differentially expressed in subcutaneous and omental depots. CGRP protein expression was higher in postmenopausal women (P < 0.05) in both fat depots. CONCLUSIONS: Our findings suggest that adipose tissue represents an important site for CGRP and ADM production and that menopause status alters their expression in abdominal fat. This offers a potential mechanism to explain the role of CGRP in menopausal vasomotor symptoms and the increased risk of cardiovascular disease in postmenopausal women.     

Calcitonin-gene related peptide (CGRP) inhibits interleukin-7-induced pre-B cell colony formation

Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with inflammatory and immunoregulatory activities. Its role in B lymphocyte development was investigated using a pre-B cell colony-forming assay. Physiological concentrations of CGRP inhibited pre-B cell responses to interleukin-7 (IL-7). Inhibition was specific in that it was blocked by the CGRP antagonist CGRP8-37. Adrenomedulin, substance P, and calcitonin had no effect on B cell precursor responses. Similar responses were observed with B220+/IgM- B cell precursors. Inhibition of IL-7 responses in B220+/IgM- cells suggests that CGRP has a direct effect on B cell precursors. Studies with cultured bone marrow-adherent cells found that CGRP also has an indirect effect on IL-7 responses. Cultured bone marrow-adherent cells were treated with CGRP for 24 h, and anti-CGRP was added to the supernatants to neutralize CGRP. Concentrations of CGRP as low as 0.01 nM induced a factor that inhibited colony formation. In contrast, CGRP did not induce an inhibitory factor in cultured bone marrow macrophages, suggesting that CGRP induces an inhibitory factor in some adherent cell other than macrophages. The results show that CGRP has both direct and indirect effects on developing B cells and support a role for CGRP as an inhibitor of early B cell development.