内源性高甘油三酯血症患者血浆VLDL、LDL及HDL对血凝的影响

目的：研究内源性高甘油三酯血症(HTG)患血浆极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL)是否发生了氧化修饰及其对血凝的影响。方法：对2l例内源性高甘油三酯血症患与2l例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆VLDL、LDL及HDL,测定这三种脂蛋白的234nm光吸收、相对电泳迁移率(REM)和硫代巴比妥酸反应物质(TBARS),分别将这三种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中,按试剂盒分别测定凝血酶原时间(PT)及活化部分凝血酶原时间(APIT)。结果：内源性HTG患血浆TG含量平均升高2．73倍,HDLC下降l.7l倍,同时LPO升高1．22倍;HTG组VLDL、LDL及HDL的REM、234nm光吸收值、TBARS含量均较对照组显增加(P＜0．01),表明内源性HTG患血浆VLDL、LDL及LDL均发生了氧化修饰生成Ox—VLDL、Ox-LDL.PT及APTT在分别加入HTG组的VLDL、LDL及HDL后均比加入相应正常组脂蛋白明显缩短(P均＜0．05)。相关分析表明,HTG组血浆VLDL及HDL相对电泳迁移率(REM)与PT呈负相关(P＜0．01)。结论：HTG患血浆VLDL、LDL及HDL发生了氧化修饰,并使PT及APTT明显缩短。     

Acute and delayed effects of prolonged exercise on serum lipoproteins

Summary To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, 13 healthy endurance-trained men were examined before and after (1 h, 20 h) a cross-country run [30 km, time: 130 (SD 7.4) min]. The data show that following acute exercise, serum triglyceride (TG) concentration were reduced (36%) as a consequence of a reduced number (31%) of very low density lipoprotein (VLDL) particles. Changes in composition of VLDL were present but less evident. In contrast to this, acute exercise did not induce significant changes in the average concentration of individual low-density lipoprotein (LDL) subfractions. However, changes in dense LDL [density (d) > 1.044 g · ml^-1}] concentration were significantly correlated to changes in serum TG: a reduction of dense LDL occurred in subjects with large reductions in serum TG. In addition, LDL composition changed significantly. Immediately (1 h) after exercise the TG content of all LDL subfractions was reduced. These reductions were significant in large (d=1.0061.037 g · ml^-1) and small LDL (1.044-1.063 g · ml -1). It can be concluded therefore from our study that acute exercise primarily altered the composition of LDL subfractions while their concentration remained stable.This paper is dedicated to Prof. Dr. J. Keul, Medical Director of our Department, on the occasion of his 60th birthday     

DMT-1在介导低密度脂蛋白氧化中的作用

目的 通过基因芯片分析发现人单核细胞THP-1氧化LDL的过程中二价金属转运蛋白1(Divalent metal transporter 1,DMT1)的mRNA表达水平显著升高.本实验通过RT-PCR和Western Blot来验证基因芯片的结果.方法用空白,LPS,LDL分别处理THP-1细胞,应用RT-PCR和Western Blot比较在LDL和LPS处理后THP-1细胞DMT-1的表达情况.结果 RT-PCR和Western Blot结果显示,在THP-1氧化LDL的过程中DMT1的表达显著升高.LDL和LPS相比,用LDL处理的THP-1细胞的DMT1的表达增加较LPS处理的明显.结论 RT-PCR和western blot证明了基因芯片的结果,在THP-1氧化LDL的过程中DMT1的表达显著升高,为临床心血管疾病的抗氧化治疗提供新的思路.     

The LDL receptor-related protein can form homo-dimers in neuronal cells

The ability of the low density lipoprotein receptor-related protein (LRP) to form homo-dimers was studied in mouse neuroblastoma and human neuroglioma cells as well as in primary cortical cultures from adult mouse brain. Homo-dimerization of LRP light chain (LC) was shown by several methods including co-immunoprecipitation, fluorescence lifetime imaging microscopy, and bimolecular fluorescence complementation assay. The requirement of intact NPXY motifs of LRP LC for homo-dimerization was ruled out by co-immunoprecipitation assay.     

Plasma lipids and lipoproteins and essential hypertension

In recent years there have been many studies demonstrating a correlation between increased arterial blood pressure and altered lipid profiles, and there has been an especially positive correlation between high cholesterol levels and blood pressure. There are differences between the various reports that are important. In our study the lipid distribution in 105 hypertensive patients with mild or moderate arterial hypertension according to WHO criteria without clinically or ultrasonographically apparent atherosclerosis was compared to the lipid distribution in 65 age-matched healthy persons. On the epidemiological level a significant, positive association was found between LDL serum levels (P 0.001), Apo B serum levels (P 0.001), serum triglyceride levels (P 0.05) and VLDL serum levels (P 0.01) and arterial hypertension. However, in contrast to recent reports, no significant difference was found between total serum cholesterol levels in normotensives and hypertensives, and there was no difference in HDL serum levels. No evidence could be found for a significant increase in lipoprotein (a) serum levels in hypertensives.Abbreviations LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein - Apo B 100 apolipoprotein B 100 - Apo A I apolipoprotein A I Correspondence to: H. Vetter     

The oxidation ratio of LDL: a predictor for coronary artery disease

Objective: Oxidized LDL cholesterol (ox-LDL-C) is considered to be a key factor of initiating and accelerating atherosclerosis (AS). The purpose of this study is to elucidate the sensitivity and specificity of ox-LDL and oxidation ratio of LDL in the diagnosis of coronary artery disease (CAD). For the first time, we investigated the ratio of ox-LDL to ALB(ox-LDL/ALB). Methods and results: Blood ox-LDL, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and albumin (ALB) were measured in patients with acute myocardial infarction (AMI, n = 80), unstable angina pectoris (UAP, n = 80), stable angina pectoris (SAP, n = 80), normal control (n = 60), and dyslipidemia control (n = 60). Ox-LDL was measured by competitive ELISA. The level of ox-LDL and oxidation ratio of LDL(ox-LDL/TC, ox-LDL/HDL-C, ox-LDL/ LDL-C and ox-LDL/ALB) were significantly higher in each diseased group than controls (P < 0.001). In CAD group, ox-LDL and oxidation ratio of LDL in subjects complicated with hypertension (HT) and/or diabetes mellitus (DM) increased further (P < 0.001). Ox-LDL/ALB in the AMI group was 7 times higher than normal control group (0.068 ± 0.017 vs 0.009 ± 0.007, P < 0.001). The area under the curve (AUC) of receiver operating characteristic curve (ROC curve) is a criterium to evaluate the accuracy of diagnosing a disease. The AUC of ROC curve of ox-LDL/TC, ox-LDL/HDL-C, ox-LDL, ox-LDL/ALB and ox-LDL/ LDL-C for diagnosing CAD were 0.975, 0.975, 0.966, 0.966, 0.957 respectively (P < 0.001). When ox-LDL/TC = 0.175, the sensitivity and specificity of diagnosing CAD were 0.917 and 0.925, which were almost equal to each other, indicating that the rates of missed diagnosis and misdiagnosis for CAD were the lowest. Conclusions: The level of ox-LDL and the ratio of ox-LDL/TC, ox-LDL/LDL-C, ox-LDL/HDL-C and ox-LDL/ALB are better biomarkers than TC, TG, HDL-C and LDL-C for discriminating between patients with coronary artery disease and healthy subjects. And patients who have a high ratio of ox-LDL /TC may have a higher risk for CAD.     

Gleichgewichtskonzentrationen einiger Plasma-Solute und Na+-Absorption bei Erhöhung des Na+-Angebotes durch Steigerung der Na+-Angebotskonzentration oder des Perfusionsvolumens/Zeit im Jejunum und Colon von Ratten

Zusammenfassung An in situ befindlichen durchbluteten Jejunum- und Colonschlingen von Ratten wurden bestimmt: die Gleichgewichtskonzentrationen von Na⁺, Cl^–, K⁺, Ca⁺⁺ und Harnstoff sowie die Abhängigkeit der Na⁺-Absorption vom Na⁺-Angebot. Dieses wurde durch Instillation 1- bis 4 fach blutisotoner NaCl-Lösungen konstanter Volumina oder durch Perfusion einer blutisotonen Ringer-Lösung mit steigendem Volumen/Zeit variiert.Die Gleichgewichtskonzentrationen im Jejunum sind: Na⁺ 76,0 mMol/l; Cl^– 70,0 mMol/l; K⁺ 4,6 mMol/l; Ca⁺⁺ 0,43 mMol/l; Harnstoff 37,8 mg/100 ml. Die analogen Zahlen für das Colon lauten: Na⁺ 13,6 mMol/l; Cl^– 10,0 mMol/l; K⁺ 12,3 mMol/l; Ca⁺⁺ 0,57 mMol/l; Harnstoff 15,9 mg/100 ml. Das Colon vermag für Na⁺ und Cl^– einen wesentlich steileren Konzentrationsgradienten aufzubauen als das Jejunum, die K⁺-Konzentration im Lumen des Colons ist dreimal höher als im Plasma, während die intraluminale Harnstoff-Konzentration der halben Plasma-Konzentration entspricht. Im Jejunum ist es dagegen für Harnstoff zum Konzentrationsausgleich Plasma/Darmlumen gekommen.Bei Instillation einer blutisotonen NaCl-Lösung in das Jejunum werden 266 Mol Na⁺/Darmschlinge/60 min und 87% der instillierten Flüssigkeit absorbiert. Werden 2- und 3fach blutisotone NaCl-Lösungen angeboten, sinkt die Na⁺-Absorptionsrate, um sich dann auf ein stabiles Niveau einzustellen. Es kommt zur Enterosorption steigender Flüssigkeitsmengen. Im Colon steigt die Na⁺-Absorptionsrate parallel der steigenden Angebotskonzentration, bei mehr als blutisotonen Instillationslösungen resultiert eine Enterosorption von Flüssigkeit.Wird das Angebot von Na⁺ und Flüssigkeit durch Variation der Perfusionsgeschwindigkeiten zwischen 6–40 ml/Std gesteigert, dann steigt im Jejunum zunächst die Absorptionsrate von Na⁺, um sich dann wiederum auf einem Plateau einzustellen. Im Colon wächst die Na⁺-Absorptionsrate kontinuierlich mit zunehmender Perfusionsgeschwindigkeit. In beiden Darmabschnitten gehen die Absorptionsraten von Na⁺ und Wasser streng parallel.Bezogen auf die Einheit der an der Sorption beteiligten Oberfläche ist die Absorptionskapazität des Colons für Na⁺ wesentlich größer als die des Jejunums.     

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.


Keywords: apolipoprotein B; hypercholesterolaemia; low density lipoprotein receptor; mutation     

Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release

Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.     

Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia

We have employed analysis of single-strand conformation polymorphisms to identify mutations in the low density lipoprotein receptor gene causing familial hypercholesterolemia. Two familial hypercholesterolemia heterozygotes had abnormal single-strand conformation polymorphism patterns of exons 4 and 8. DNA sequencing revealed that the abnormal pattern of exon 4 was due to heterozygosity (G/T) at nucleotide 502. Nucleotide 502 is the first base of codon 147, and the G→T mutation (D147Y) changes this codon from Asp_GAC to Tyr_UAC. The abnormal pattern of exon 8 was due to heterozygosity (A/G) at nucleotide 1097. Nucleotide 1097 is the second base of codon 345, and the A→G mutation (Q345R) changes this codon from Gln_CAG to Arg_CGG- Based upon screening of 437 unrelated familial hypercholesterolemia heterozygotes, both D147Y and Q345R account for about 0.5% of the mutations causing familial hypercholesterolemia in Norway.     

Die Verteilung von J131-Albumin in der Niere von Ratten und Kaninchen

Summary The renal uptake and intrarenal distribution of J¹³¹-Albumin has been studied after i.v. injection in rats and rabbits by counting and frozen section radioautography. In kidney cortex radioalbumin is distributed not only intravasally and interstitially but also located intracellularly to a significant degree. Concepts based on the assumption of exclusive extracellular distribution of albumin-such bumin-such as concerning the intrarenal hematocrit or the significance of the interstitial cortical albumin-therefore might need reevaluation. In contrast to renal cortex papilla and outer medulla vascular zones showed only extracellular radioalbumin distribution with probably high concentrations in the interstitial compartment. Radioalbumin distribution kinetics in the various regions of the kidney were different; this difference might lead to errors concerning the endogenous albumin-pool, if conclusions are based without differentiation on total renal activity only.

Mit Unterstützung des Bundesministeriums für Bildung und Wissenschaft.     

银杏内酯B抑制非酒精性脂肪性肝病大鼠肝脏极低密度脂蛋白输出

目的:探讨银杏内酯B对高脂高糖饮食诱导的非酒精性脂肪性肝病大鼠肝脏极低密度脂蛋白(VLDL)输出的影响.方法:72只SD大鼠适应性喂养10 d后按照随机数字表法分为正常对照(CON)组、模型(MOD)组、阳性药物辛伐他汀(SIM)组及银杏内酯B低、中和高剂量治疗组,每组12只.除对照组外,大鼠采用高脂高糖饮食喂养12周...     

15N-Tracertechnische Untersuchungen zum Eiweißstoffwechsel bei Arteriosklerosepatienten

Summary The incorporation of the stable isotope¹⁵N in plasma proteins and blood cells after oral application of 3 g¹⁵NH₄Cl (95 At%¹⁵N) per 70 kg body weight was followed up in 11 patients with ischemic heart disease or peripheral arteriosclerosis and in 7 healthy control subjects. Preliminary results indicate that the turnover of plasma protein, especially fibrin, is elevated in patients with arteriosclerosis. Investigations of platelets intimate a decreased turnover of platelet protein in patients with arteriosclerosis as compared to control subjects. Possible reasons for these alterations are discussed.

     

Wellness in community living adults: the Weigh to Life program

Objective

To examine physiological and health-related quality of life (HRQOL) outcomes in community living adults attending a 12-week combined lifestyle wellness program.

Methods

A sample of overweight and obese adults (n = 319) and a subgroup who also had diabetes (n = 46 of 319) were studied. The program focuses on dietary, physical activity, and behavioral strategies to promote cardiovascular health. Baseline and 12-week measures were obtained.

Results

In the total sample, all physiological and HRQOL outcomes improved (p < .05), except HDL. High attendance was associated with the highest weight loss. In the diabetic subgroup, weight, steps/day, low density lipoprotein, and most aspects of HRQOL improved significantly.

Conclusion

Physiological and HRQOL benefits can be gained from a 12-week combined lifestyle program; greater benefits were obtained with higher attendance. Although the diabetic subgroup was not large, positive outcomes were realized.

Practice implications

The 12-week combined lifestyle program shows promise for improving outcomes in community living overweight and obese adults who may also be diabetic. By attending class, participants are reminded about strategies they are to apply during the 12-week program and, by program end, they are equipped with a tool kit of strategies for use in everyday life.     

Phospholipid Hydrolysis with Phospholipases A2 and C Impairs Apolipoprotein B-100 Conformation on the Surface of Low Density Lipoproteins by Reducing Their Association Resistance

Modification of apolipoprotein B-100 conformation on the surface of LDL isolated from human blood was demonstrated by enzyme immunoassay with a panel of monoclonal antibodies to this protein. The study by the light transmission fluctuation method showed that incubation of LDL with phospholipases A₂ or C led to association of LDL particles. This lipolytic modification seems to impair LDL surface properties inducing association of these particles, which can play an important role in lipid accumulation in the vascular wall and at early stages promote the development of atherosclerosis. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 10, pp. 418–422, October, 2005     

PKC参与化学修饰的LDL对ABCA1表达和功能的调节

目的 探讨PKC信号途径对oxLDL和acLDL诱导的小鼠巨噬细胞ABCAl表达的影响。方法 分别以100μg/ml acLDL和oxLDL温育小鼠巨噬细胞系RAW264.7细胞24 h,同时加入PKC信号途径的激活剂(PMA)或抑制剂(GF109203X),应用胆固醇外排实验、半定量RT-PCR和Western印迹,检测小鼠巨噬细胞内ABCAl功能、mRNA及蛋白质表达的水平。结果 1.0 μmol/L GF109203X可分别使aeLDL孵育组的胆固醇外排率下降至对照组的56.0％,ABCA1 mRNA水平下降至(54.0±8.2)％,蛋白质水平下降至(68.1±2.0)％;oxLDL孵育组的胆固醇外排率下降至对照组的47.0％,ABCA1 mRNA水平下降至(43.0±5.0)％,蛋白质水平下降至(73.0±10.0)％。160 nmol/L PMA作用24 h可分别使acLDL孵育组的胆固醇外排率升高至134.0％,oxLDL孵育组升高至125.1％;ABCA1 mRNA水平升高至(211.0±17.0)％,蛋白质水平升高至(305.0±21.0)％。结论 PKC信号途径在oxLDL和acLDL对小鼠巨噬细胞内ABCA1表达调控中发挥作用,该信号途径的激活可上调ABCA1的表达,促进ABCA1介导的胆固醇外排。     

DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia

DNA samples from 25 unrelated Danish patients with familial hypercholesterolemia (FH) were screened by Southern blot hybridization to detect gross alterations in the low density lipoprotein (LDL) receptor gene. Three FH-patients were found to have a deletion. Two of these delete part of the cysteine rich domain, which comprises the ligand binding region of the LDL-receptor. The third deletion encompasses coding regions for the cytoplasmic part of the receptor. As two of these deletions could be equivalent to previously described LDL-receptor gene alterations, these data seem to support a notion of recombination hot spots which involve Alu-sequences.     

Mouse hepatitis virus pathogenesis in the central nervous system is independent of IL-15 and natural killer cells

Infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an acute encephalomyelitis associated with demyelination. T cells are critical in controlling viral replication, but also contribute to central nervous system (CNS) pathogenesis. To reveal a role for innate effectors in anti-viral immunity and neurological disease, JHMV pathogenesis was studied in mice deficient in interleukin-15 (IL-15-/-) and natural killer (NK) cells. Clinical disease, CNS inflammation and demyelination in infected IL-15-/- mice were similar to wild-type mice. Despite the absence of NK cells and suboptimal CD8+ T cell responses, IL-15-/- mice controlled JHMV replication as efficiently as wild-type mice. Similar kinetics of class I and class II upregulation on microglia further suggested no role of NK cells in regulating major histocompatibility complex (MHC) molecule expression on resident CNS cells. IL-15 and NK cells thus appear dispensable for anti-viral immunity and CNS pathogenesis during acute JHMV infection.     

Untersuchungen zur fluorescenz- und elektronenmikroskopischen Darstellung von 5-Hydroxytryptamin (5-HT) im Pineal-Organ von Lacerta viridis und L. muralis

Zusammenfassung Es wurden Pinealorgane (Epiphysis cerebri) ausgewachsener Eidechsen (Lacerta viridis und Lacerta muralis) mit der Falck-Hillarp Methode und dem Elektronenmikroskop untersucht, um 5-Hydroxytryptamin (5-HT) in den sekretorischen Pinealzellen zu bestimmen und zu lokalisieren. Die in dem Pinealorgan enthaltene Menge an 5-HT ist sehr groß (Gesamtmenge in Gehirn = 0,1998 g; Gesamtmenge in Pinealorgan = 0,0869 g=43%). Beim Vergleich der durch Fluorescenz- und Elektronenmikroskopie gewonnenen Resultate ergab sich, daß Pinealocyten zwei Formen von 5-HT enthalten. Die Hauptmenge ist in Granula mit einem durchschnittlichen Durchmesser von 1337±42 Å (L. muralis) lokalisiert, die von einer Elementarmembran umgeben sind, wodurch sie vom Cytoplasma getrennt sind (große, granulierte Vesikel zwischen 600 und 3000 Å). Dieser intravesiculäre 5-HT-Pool ist gegen Reserpinbehandlung relative resistent und scheint außerdem sehr fest an eine Protein-Matrix der Granula gebunden zu sein. Sogar nach 2 Dosen von 10 mg/kg Reserpin findet man nur eine Abnahme der relativen Fluorescenzintensität um etwa 50%. Das entspricht einer geringen, aber doch signifikanten Durchmesserabnahme des granulären Gehaltes nach Reserpin-Vorbehandlung, wogegen 2 Dosen von 300 mg/kg Nialamid keine sichtbaren Veränderungen an den Granula hervorrufen. Die zweite 5-HT-Form ist Bestandteil eines schnell verfügbaren, extravesiculären Pools, der über das gesamte Cytoplasma verteilt ist. Ab- und Zunahme der gelben Fluorescenz nach Reserpin oder Nialamid-Behandlung dürften im wesentlichen auf Einwirkung auf diesen extravesiculären Pool zurückzuführen sein. Elektronenmikroskopisch ist diese 5-HT Form schwer zu lokalisieren; jedoch führt eine Vorbehandlung mit Nialamid und 5-Hydroxytryptophan (5-HTP) zu einem starken Anstieg des extravesiculären Pools, in dessen Folge Orte mit hohen Konzentrationen an 5-HT-haltigen Substanzen sichtbar werden. Unter normalen Bedingungen stehen beide Poole in einem Gleichgewicht, und zwar in einer Weise, daß die Menge an extravesiculären 5-HT niedrig aber konstant gehalten wird.

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Studies on the fluorescence and electronmicroscopic identification of 5-hydroxytryptamine (5-HT) in the pineal organ of lacerta viridis and L. muralis

Summary The pineal organ (epiphysis cerebri) of adult lizards (Lacerta viridis and Lacerta muralis) has been studied by means of Falck's and Hillarp's method and electron microscopically with the aim to detect and localize 5-hydroxytryptamine (5-HT) in secretorial pinealocytes. The amount of 5-HT concentrated in the pineal organ is extremly high (total amount per brain = 0.1998 g; total amount per pineal organ = 0.0869 g=43%). Comparison of the results obtained by fluorescence and electron microscopy demonstrates that pinealocytes contain two types of 5-HT. The major amount is localized in granules with a diameter of 1337±42 Å (L. muralis). They are surrounded by a unit membrane separating the interior from the cytoplasm (=large granulated vesicles ranging between 600 and 3000 Å). This intravesicular pool of 5-HT is relatively resistent towards reserpine treatment and seems to be tightly bound to a protein matrix of the granules. Even after 2 doses of 10 mg/kg reserpine there is only a decrease of the relative fluorescence intensity of about 50%. That corresponds to a small but significant decrease in the diameter of the granular content after reserpine pretreatment whereas 2 doses of 300 mg/kg nialamide do not produce any observable alteration of the granules. The second type of 5-HT constitutes an easily available extravesicular pool spread over the cytoplasm. Increase and decrease of the yellow fluorescence after nialamid and reserpine treatment might be largely due to the influence on this extravesicular pool. Electron microscopically this type of 5-HT is difficult to localize; pretreatment with nialamide and 5-hydroxytryptophane (5-HTP), however, considerably increases the extravesicular pool and sites of large concentrations of 5-HT containing substances become visible. Under normal conditions both pools are balanced in such a way as to keep down and hold constant the amount of extravesicular 5-HT.

Mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft.