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PROPERTIES OF RENIN GRANULES ISOLATED FROM RAT-KIDNEY

MOLECULAR AND CELLULAR ENDOCRINOLOGY 1976年第5期5卷 331-337页

作者： HONG, JS POISNER, AM UNIV KANSAS MED CTR COLL HLTH SCI DEPT PHARMACOL KANSAS CITY KS 66103 USA UNIV KANSAS HOSP KANSAS CITY KS 66103 USA

Renin granules from rat kidney prepared at ***. C show greater stability at ***. C than at ***. C when incubated in ionic medium. The sum of the renin in the supernatant fluid plus that in the pellet was the same at ***. as at ***. C, ruling out the possibility that the extra release at ***. C merely represented greater stability of free renin at ***. C. In common with other secretory granules, renin granules were most stable at pH 6.0 and were osmotically sensitive. In contrast to neurosecretory and chromaffin granules, renin granules were stabilized by Mg-ATP in ionic medium. This result is similar to studies by others on lysosomes. The renin granule membrane shares many of the properties of other granule membranes. Some of these properties (temperature and pH lability) will have to be considered in the design of future experiments on renin storage and release.

关键词：腺苷三磷酸/药理学细胞分级分离细胞质颗粒/药物作用细胞质颗粒/代谢细胞质颗粒/超微结构氢离子浓度肾/药物作用肾/代谢镁/药理学容积渗克分子浓度肾素/分离和提纯肾素/代谢温度动物大鼠

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Role of actin cortex in the subplasmalemmal transport of secretory granules in PC-12 cells

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BIOPHYSICAL JOURNAL 2000年第6期78卷 2863-2877页

作者： Lang, T Wacker, I Wunderlich, I Rohrbach, A Giese, G Soldati, T Almers, W Oregon Hlth Sci Univ Vollum Inst Portland OR 97201 USA Max Planck Inst Biophys Chem D-37077 Gottingen Germany Max Planck Inst Med Forsch D-69120 Heidelberg Germany European Mol Biol Lab D-69012 Heidelberg Germany

In neuroendocrine PC-12 cells, evanescent-field fluorescence microscopy was used to track motions of green fluorescent protein (GFP)-labeled actin or GFP-labeled secretory granules in a thin layer of cytoplasm where cells adhered to glass. The layer contained abundant filamentous actin (F-actin) locally condensed into stress fibers. More than 90% of the granules imaged lay within the F-actin layer. One-third of the granules did not move detectably, while two-thirds moved randomly;the average diffusion coefficient was 23 x 10(-4) mu m(2)/s. A small minority (<3%) moved rapidly and in a directed fashion over distances more than a micron. Staining of F-actin suggests that such movement occurred along actin bundles. The seemingly random movement of most other granules was not due to diffusion since it was diminished by the myosin inhibitor butanedione monoxime, and blocked by chelating intracellular Mg2+ and replacing ATP with AMP-PNP. Mobility was blocked also when F-actin was stabilized with phalloidin, and was diminished when the actin cortex was degraded with latrunculin B. We conclude that the movement of granules requires metabolic energy, and that it is mediated as well as limited by the actin cortex. Opposing actions of the actin cortex on mobility may explain why its degradation has variable effects on secretion.

关键词：肌动蛋白类/化学肌动蛋白类/生理学肌动蛋白类/超微结构腺苷三磷酸/生理学腺苷酰亚氨二磷酸/药理学细胞质颗粒/药物作用细胞质颗粒/生理学二乙酰/类似物和衍生物二乙酰/药理学绿色荧光蛋白质类动力学发光蛋白质类/分析镁/生理学运动(Movement) PC12细胞重组融合蛋白质类/分析动物大鼠

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Corticosterone replacement restores normal morphological features to the hippocampal dendrites, axons and synapses of adrenalectomized rats

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JOURNAL OF NEUROCYTOLOGY 1999年第7期28卷 541-558页

作者： Sousa, N Madeira, MD Paula-Barbosa, MM Porto Med Sch Dept Anat P-4200319 Porto Portugal

A thorough evaluation of hippocampal dendrites, axons and synaptic contacts has not been undertaken following prolonged periods of absence of corticosteroids despite the marked granule cell loss which occurs in the dentate gyrus of adrenalectomized rats. Thus, we have applied morphometric techniques to analyse the dendrites of granule and pyramidal cells, the mossy fiber system, and the number and morphology of synapses between the mossy fibers and the excrescences of CA3 pyramidal cells in rats submitted to different periods of adrenalectomy. In addition, to search for the presence of neuritic reorganisation in the hippocampal formation once normal corticosteroid levels were re-established, we incorporated in this study a group of rats replaced with corticosterone one month after adrenalectomy. The results obtained in adrenalectomized rats showed a striking impoverishment of the dendrites of surviving granule cells, subtle alterations in the apical dendritic arborization of CA3 pyramidal cells and no changes in the apical dendrites of CA1 pyramidal cells. In addition, in adrenalectomized rats there was a progressive reduction in the total number of synapses established between mossy fibers and CA3 pyramids, as a consequence of a reduction in the volume of the suprapyramidal part of the mossy fiber system, and profound changes in the morphology of mossy fiber terminals and CA3 dendritic excrescences. A remarkable reorganisation of neurites was found to occur following the administration of low doses of corticosterone, completely reversing the adrenalectomy-induced synaptic loss and partially restoring the morphology of hippocampal axons and dendrites. These plastic mechanisms provide a sound structural basis for the reversibility of cognitive deficits observed after corticosterone administration to adrenalectomized rats.

关键词：肾上腺切除术方差分析轴突/药物作用轴突/超微结构皮质酮/药理学细胞质颗粒/药物作用细胞质颗粒/超微结构树突/药物作用树突/超微结构齿状回/细胞学齿状回/药物作用海马/细胞学海马/药物作用神经元/药物作用神经元/超微结构锥体细胞/药物作用锥体细胞/超微结构大鼠 Wistar 突触/药物作用突触/超微结构动物男(雄)性大鼠

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DAMAGE TO REISSNERS MEMBRANE IN GUINEA-PIG COCHLEA FOLLOWING ACUTE ATOXYL INTOXICATION

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ACTA OTO-LARYNGOLOGICA 1976年第5-6期81卷 415-423页

作者： ANNIKO, M HUDDINGE SJUKHUS KAROLINSKA INST DEPT OTOLARYNGOL STOCKHOLM SWEDEN KAROLINSKA INST KING GUSTAV V RES INST S-10401 STOCKHOLM SWEDEN

The ototoxic effects of the arsenic compound atoxyl was demonstrated earlier by Anniko and Wersall in the stria vascularis of the guinea pig cochlea. The morphological degeneration was studied at the ultrastructural level after damaging the Reissner''s membrane experimentally. In acute atoxyl intoxication the 1st signs of degeneration appeared after approximately 12 h. After 24 h the membrane may be markedly degenerated. Both the epithelial and mesothelial cells became vacuolized;the mitochondria lost their internal structure and became swollen, and lipid granules were found in the cytoplasm. Mesothelial cells were damaged to a lesser extent than the epithelial cells in the same specimen.

关键词：砷中毒耳蜗/药物作用耳蜗/超微结构细胞质颗粒/药物作用细胞质颗粒/超微结构上皮细胞上皮/超微结构线粒体/药物作用线粒体/超微结构 Corti器/药物作用 Corti器/超微结构动物豚鼠

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Stimulation of Ca²⁺-independent exocytosis in rat pituitary gonadotrophs by G-protein

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JOURNAL OF PHYSIOLOGY-LONDON 2000年第1期526卷 99-108页

作者： Tse, FW Tse, A Univ Alberta Dept Pharmacol Edmonton AB T6G 2H7 Canada Univ Alberta Div Neurosci Edmonton AB T6G 2H7 Canada

1. We employed the whole-cell recording technique in conjunction with fluorometry to measure cytosolic Ca2+ concentration ([Ca2+],) and exocytosis (capacitance measurement) in single, identified rat gonadotrophs. 2. Direct activation of G-protein (via intracellular dialysis of non-hydrolysable analogues of GTP, but not of GDP) triggered a slow rise in capacitance even in the presence of a fast intracellular Ca2+ chelator. 3. The head-spectrum kinase inhibitors H7 and staurosporine did not prevent this Ca2+- independent exocytosis, ruling out the involvement of the cAMP and PKC pathways. 4. AIF(4)(-);a potent stimulator of heterotrimeric G-proteins, failed to stimulate any exocytosis when the intracellular Ca2+ store was depleted, implicating the involvement of AIF(4)(-)- insensitive G-protein(s). 5. Maximal stimulation of Ca2+-independent exocytosis by GTP analogues did not reduce the number of readily releasable granules that were available subsequently for Ca2+-dependent release. 6. The last finding raises the possibility that the G-protein-stimulated Ca2+-independent exocytosis may regulate a pool of granules that is distinct fr om the Ca2+-dependent pool.

关键词： 1-(5-异喹啉磺酰基)-2-甲基哌嗪/药理学铝化合物/药理学钙/代谢钙转运ATP酶类/拮抗剂和抑制剂环AMP/代谢细胞质颗粒/药物作用细胞质颗粒/代谢胞质溶胶/代谢依他酸/类似物和衍生物依他酸/药理学酶抑制剂/药理学胞吐作用/药物作用胞吐作用/生理学氟化物/药理学荧光计 GTP结合蛋白质类/代谢 GTP结合蛋白质类/药理学鸟苷5'-O-(3-硫代三磷酸)/药理学鸟苷酰亚胺二磷酸/药理学膜片钳术光解垂体前叶/细胞学垂体前叶/药物作用垂体前叶/代谢蛋白激酶C/拮抗剂和抑制剂星状孢子素/药理学动物男(雄)性大鼠

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CATECHOLAMINE SYNTHESIS, STORAGE AND RELEASE IN ADRENAL-MEDULLA AND WHOLE BRAIN DURING ACUTE AND CHRONIC METHADONE ADMINISTRATION

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BIOCHEMICAL PHARMACOLOGY 1976年第22期25卷 2523-2527页

作者： SLOTKIN, TA LAU, C BARTOLOME, M SEIDLER, FJ DUKE UNIV DEPT PHYSIOL & PHARMACOL DURHAM NC 27710 USA

Methadone was administered daily to rats and the adrenals were analyzed for catecholamines (CA), tyrosine hydroxylase (TH) activity and dopamine .beta.-hydroxylase (DBH) activity. Four hours after 2.5 mg/kg, CA and DBH were depleted significantly but recovered to normal by 24 h. After 6 days of treatment, adrenal catecholamines were elevated above controls;24 h after increasing the dose to 10 mg/kg, CA and DBH again declined, and TH was elevated. Chronic administration of 10 or 25 mg/kg led to restoration or elevation of adrenal CA and marked increases in TH and DBH. While methadone increased the rate of formation of new adrenal storage vesicles, it also inhibited CA uptake into the vesicles, an effect which was also observed with methadone in vitro. Similarly, methadone in vitro inhibited amine uptake into crude whole brain synaptosomes, but the effect was not observed after acute or chronic administration in vivo. Methadone, like morphine, stimulates the sympatho-adrenal axis, but that unlike morphine, methadone exerts a direct effect on adrenal storage vesicles.

关键词：肾上腺髓质/药物作用肾上腺髓质/代谢体重脑/药物作用脑/代谢儿茶酚胺类/生物合成细胞质颗粒/药物作用细胞质颗粒/代谢多巴胺β羟化酶/代谢肾上腺素/代谢美沙酮/药理学奥克巴胺/生物合成器官测量突触体/药物作用突触体/代谢酪胺/代谢酪氨酸单氧化酶/代谢动物男(雄)性大鼠

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VESICULAR BINESIS - GLUCOSE EFFECT ON INSULIN SECRETORY VESICLES

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SCIENCE 1975年第4172期187卷 177-179页

作者： GABBAY, KH KORFF, J SCHNEEBERGER, EE CHILDRENS HOSP MED CTRDEPT MEDENDOCRINE DIVCELL BIOL LABBOSTONMA 02115 HARVARD UNIV MED SCHDEPT PEDIATBOSTONMA 02115 HARVARD UNIV MED SCHDEPT PATHOLBOSTONMA 02115 CHILDRENS HOSP MED CTRDEPT PATHOLENDOCRINE DIVCELL BIOL LABBOSTONMA 02115

Binesis is a process whereby the membrane of the insulin secretory vesicle in the beta cell forms a lingula that indents the vesicular membrane of an adjoining secretory vesicle or the plasma membrane. Vesicular binesis in beta cells increases when islets of Langerhans are incubated at a stimulatory glucose concentration (300 milligrams per 100 milliliters). These vesicular membrane alterations may be the morphological concomitants of activation of the insulin secretory vesicle, and indicate an active role for the vesicle and its membrane in the release mechanism.

关键词：细胞质颗粒/药物作用胞吐作用/药物作用葡萄糖/药理学胰岛素/分泌胰岛/分泌胰岛/超微结构膜/药物作用显微镜检查电子分泌率/药物作用刺激化学性动物大鼠

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Sorting of a constitutive secretory protein to the regulated secretory pathway of exocrine cells

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1999年第2期257卷 545-548页

作者： Gorr, SU Moore, YR Univ Louisville Hlth Sci Ctr Dept Biol & Biophys Sci Sch Dent Louisville KY 40292 USA

Exocrine cells secrete granule proteins by regulated or constitutive-like secretory pathways, It is thought that all secretory proteins can enter immature secretory granules in exocrine cells. To test this hypothesis, we expressed the constitutive secretory protein secreted alkaline phosphatase (SEAP) in the exocrine cell line AR42J and compared its secretion to that of amylase, an endogenous regulated secretory protein. Secretion of SEAP and amylase were stimulated about 1.5-fold by substance P and 2-fold by barium chloride. In dexamethasone-treated cells, SEAP and amylase secretion were stimulated about 1.8-fold by substance P, 5-fold by barium chloride, and 4-fold by cholecystokinin-8. Cycloheximide reduced basal secretion of SEAP and amylase by 50%, increasing cholecystokinin-stimulated secretion to about 10-fold. Sodium butyrate induced expression of SEAP 2-fold but had no effect on stimulated secretion. These results suggest that SEAP is stored in secretory granules in AR42J cells. (C) 1999 Academic Press.

关键词：碱性磷酸酶/遗传学碱性磷酸酶/代谢碱性磷酸酶/分泌淀粉酶类/代谢淀粉酶类/分泌钡化合物/药理学丁酸盐类/药理学细胞系氯化物/药理学胆囊收缩素/药理学放线菌酮/药理学细胞质颗粒/药物作用细胞质颗粒/代谢细胞质颗粒/分泌地塞米松/药理学胰腺/细胞学胰腺/药物作用胰腺/代谢胰腺/分泌氯化钾/药理学 P物质/药理学十四酰佛波乙酯/药理学转染动物大鼠

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Methaqualone derivatives are potent noncompetitive AMPA receptor antagonists

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 2000年第11期10卷 1203-1205页

作者： Chenard, BL Menniti, FS Pagnozzi, MJ Shenk, KD Ewing, FE Welch, WM Pfizer Inc Div Cent Res Groton CT 06340 USA

关键词：细胞培养的小脑/药物作用小脑/超微结构细胞质颗粒/药物作用兴奋性氨基酸拮抗剂/化学兴奋性氨基酸拮抗剂/药理学甲喹酮/类似物和衍生物甲喹酮/药理学受体 AMPA/拮抗剂和抑制剂动物大鼠

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PARATHYROID MORPHOLOGY IN GERBILS AFTER THYROIDECTOMY AND CALCIUM ADMINISTRATION

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ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA SECTION A-PATHOLOGY 1975年第5期83卷 539-549页

作者： BOQUIST, L FAHRAEUS, B UNIV UMEA DEPT UROLUMEASWEDEN UNIV UMEA DEPT PATHOLUMEASWEDEN

Morphological studies of the parathyroid glands from adult Mongolian gerbils in which hypercalcaemia had been induced by thyroidectomy and calcium injections for 2-19 days were carried out. The potassium pyro-antimonate technique and subsequent X-ray analysis of the precipitates were used for ultrastructural localization of cations. Ultrastructurally, most (suppressed) chief cells exhibited a dense cytoplasm, medium-sized or large mitochondria, glycogen particles, inconspicuous endoplasmic reticulum and Golgi complex, calcium-containing precipitates mainly in mitochondria and nuclei, and sometimes also lysosomal bodies and accumulations of secretory granules which occasionally seemed to be discharged into cytoplasmic vacuoles. A few parenchymal cells showed a low cytoplasmic density, few organelles, and structurally altered mitochondria, occasionally with associated smooth-surfaced vacuoles. These cells possessed calcium-containing precipitates in mitochondria, smooth-surfaced vacuoles, and also diffusely in the cytosol. It is concluded, that, in the main part of the parenchymal cells, the hypercalcaemia had resulted in a suppression primarily of the synthetic and later also of the secretory activity, and that the calcium-containing precipitation is different in the chief cell variants.

关键词：钙/药理学细胞膜/药物作用细胞膜/超微结构细胞核/药物作用细胞核/超微结构细胞质/药物作用细胞质/超微结构细胞质颗粒/药物作用细胞质颗粒/超微结构内质网/药物作用内质网/超微结构沙鼠亚科高尔基体/药物作用高尔基体/超微结构线粒体/药物作用线粒体/超微结构甲状旁腺/药物作用甲状旁腺/超微结构甲状腺切除术动物女(雌)性男(雄)性

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