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外周型苯二氮䓬受体:新生大鼠全身切片的放射自显影定位

Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats.

作者信息

Anholt R R, De Souza E B, Oster-Granite M L, Snyder S H

出版信息

J Pharmacol Exp Ther. 1985 May;233(2):517-26.

PMID:2987488
Abstract

We have developed a procedure that allows the autoradiographic localization of benzodiazepine receptors in whole-body sections of neonatal rats. Central-type benzodiazepine receptors, visualized with [3H]methylclonazepam, are restricted to nervous tissue. In contrast, peripheral-type benzodiazepine receptors, visualized with [3H]Ro5-4864, occur widely, but with discrete localizations throughout the body. Peripheral-type benzodiazepine receptors are most concentrated in the adrenal cortex and the skin. Substantial levels of these receptors are also evident in the heart, the salivary glands, discrete regions of the kidney, the epithelium of the lung, the nasal and lingual epithelia, the lining of the pulmonary arteries, the thymus, the hair follicles of the vibrissae, the tooth buds and the bone marrow. Considerable binding of [3H]Ro5-4864 is observed in the brown fat pads, the liver and the spleen, but high levels of nonspecific binding preclude accurate evaluation of the actual specific binding in these organs. Only low levels of [3H]Ro5-4864 binding sites are found in the brain and they are virtually undetectable in the skeletal muscle, the eye, the inner ear and the gastrointestinal tract. High levels of peripheral-type benzodiazepine receptor appear present in tissues that derive their metabolic energy primarily from oxidative phosphorylation, whereas only low levels are present in tissues that can derive their metabolic energy largely from glycogenolysis. Association of these receptors with mitochondria and a possible role in modulation of energy metabolism is suggested further by the observation that the histochemically visualized distribution of cytochrome oxidase activity overlaps the autoradiographic pattern of [3H]Ro5-4864 binding sites.

摘要

我们已开发出一种程序,可对新生大鼠全身切片中的苯二氮䓬受体进行放射自显影定位。用[³H]甲基氯硝西泮显示的中枢型苯二氮䓬受体仅限于神经组织。相比之下,用[³H]Ro5 - 4864显示的外周型苯二氮䓬受体广泛分布于全身,但定位离散。外周型苯二氮䓬受体在肾上腺皮质和皮肤中最为集中。在心脏、唾液腺、肾脏的离散区域、肺上皮、鼻和舌上皮、肺动脉内膜、胸腺、触须毛囊、牙胚和骨髓中也明显存在大量此类受体。在棕色脂肪垫、肝脏和脾脏中观察到[³H]Ro5 - 4864有相当程度的结合,但高水平的非特异性结合妨碍了对这些器官中实际特异性结合的准确评估。在大脑中仅发现低水平的[³H]Ro5 - 4864结合位点,而在骨骼肌、眼睛、内耳和胃肠道中几乎检测不到。外周型苯二氮䓬受体在主要从氧化磷酸化获取代谢能量的组织中含量较高,而在主要从糖原分解获取代谢能量的组织中含量较低。细胞色素氧化酶活性的组织化学可视化分布与[³H]Ro5 - 4864结合位点的放射自显影模式重叠这一观察结果进一步表明这些受体与线粒体有关联,并可能在能量代谢调节中发挥作用。

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