二、通过细胞内受体介导的信号传递 细胞内受体 亲脂 甾类激素和甲状腺素

Signal transdution mediated by the receptors within cells A. Nuclear receptors for steroid, retinoic acid类维生素A, vitamin D and thyroid hormones

甾类激素穿过细胞膜 胞内受体结合进入细胞核 与受体依赖的转录增强子DNA序列相结合 增强相关基因的转录水平 产生相应的蛋白质

类固醇类激素靶细胞有一万个相应的受体。受体有明显的同源性。 受体在各种细胞中一样，但细胞的反应不同有人认为，有特异性基因调节蛋白，是这种蛋白使不同细胞对相同受体信使复合体有不同的反应。如睾丸素。 睾丸雌性化综合征。（医学332）

化学信号分子 胞内受体 化学信号分子胞内受体复合物

甾类激素受体图 基因活化区 与DNA结合区 受体结构 激素结合位点 扩散进入 穿过核膜孔 核膜 复合体 增强子 基因 基因 启动子 抑制蛋白 化学信号分子 基因活化区 与DNA结合区 受体结构 激素结合位点 扩散进入 抑制蛋白 化学信号分子胞内受体复合物 穿过核膜孔 核膜 复合体 增强子 基因 基因 启动子

信号分子除 蛋白质 肽 氨基酸 脂肪酸 核苷酸 甾类 萜类等。 又发现一些可溶性气体也是信号分子如 NO CO2 当前对细胞因子和NO备受瞩目。NO是一种自由基性质的气体，具有脂溶性，NO在细胞外极不稳定。NO生成细胞是血管内皮细胞。NO是以局部介质发挥作用的。靶细胞内鸟苷酸环化酶的激活是ON发挥作用的主要机制。

The Nobel Prize in Physiology or Medicine 1998

The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, has awarded the Nobel Prize in Physiology or Medicine for 1998 to Robert F Furchgott, Louis J Ignarro and Ferid Murad for their discoveries concerning "the nitric oxide as a signalling molecule in the cardiovascular system".

Robert F Furchgott, born 1916 Dept Robert F Furchgott, born 1916 Dept. of Pharmacology, SUNY Health Science Center New York

Louis J Ignarro, born 1941 Dept Louis J Ignarro, born 1941 Dept. of Molecular and Medical Pharmacology UCLA School of Medicine Los Angeles

Ferid Murad, born 1936 Dept. of Integrative Biology Pharmacology and Physiology University of Texas Medical School, Houston

A New Principle Nitric Oxide, NO, is a short-lived, endogenously produced gas that acts as a signalling molecule in the body. Signal transmission by a gas, produced by one cell, which penetrates membranes and regulates the function of other cells is an entirely new principle for signalling in the human organism.

Furchgott's sandwich Robert F Furchgott showed that acetylcholine-induced relaxation of blood vessels was dependent on the endothelium内皮. His "sandwich" experiment set the stage for future scientific development. He used two different pieces of the aorta主动脉; one had the endothelial layer intact, in the other it had been removed.

Ignarro's spectral analysis Louis Ignarro reported that EDRF(内皮细胞松弛因子Undothe1MIn-derived relaxing factor, EDRF) relaxed blood vessels. He also identified EDRF as a molecule by using spectral analysis of hemoglobin血红蛋白.

When hemoglobin was exposed to EDRF, maximum absorbance moved to a new wave-length; and exposed to NO, exactly the same shift in absorbance occurred! EDRF was identical with NO. A new principle for signalling between human cells was discovered.

Spectrophotometry,分光光度技术 Hemoglobin (yellow) exposed to endothelial cells that were stimulated to produce EDRF (green)

Hemoglobin (yellow) directly exposed to NO (green) The shift of absorption curves is identical, hence EDRF is NO