肾上腺皮质球状带细胞的电兴奋性与醛固酮分泌:离子通道的作用

醛固酮是肾上腺皮质球状带(ZG)细胞产生的类固醇类激素,对体液电解质平衡和血压稳定起着关键调控作用。醛固酮生成是一个钙离子依赖性的过程,离子通道在这一过程中扮演着关键角色。临床上发现的原发性醛固酮增多症大多与离子通道的突变有关。最近ZG细胞独特的rosette结构与其电兴奋性的关系引起了更多研究兴趣。阐明rosette与ZG细胞电兴奋性以及醛固酮分泌之间的关系,有助于更深入地了解调节醛固酮分泌的机制,为原发性醛固酮增多症的发病机制提供新见解。

BENZODIAZEPINE RECEPTORS IN ISOLATED ADRENAL GLOMERULOSA CELLS

In our experiments the isolated rat adrenal glomerulosa cells displayed perlpheral-type benzodiazepine receptors, which could bind to [~3H] PKl1195 with an apparent equilibrium dissociation constant (KD) of 9.4±2.8 nmol/L and a maximal binding capacity (B_(max)) of 5.6q-1.8 pmol/10~6 cells. The effects of five ligands: PKl1195, Ro5--4846, flunitrazepam, diazepam and clonazepam on aldosterone secretion responses of isolated glomerulosa cells to anglotensin Ⅱ or extracellular potassium ions were observed. The logarithm of EO_(50) for these ligands as stimulators was well correlated with the logarithm of their Ki value for [~3H] PK11195 binding, suggesting that the stimulative effects might be mediated by the benzodiazepine receptor in isolated glomerulosa cells.

Histological Study on the Adrenal Gland of Zebra

In order to explore the histological structure of zebra and to protect en- dangered species diversity, it is especially important to study the zebra adrenal his- tological structure. 2 zebra adrenals were studied by means of histological methods. The adrenal gland tissues were dissected into serial paraffin sections at the thick- ness of 3 μm. After HE and Masson staining, they were observed and photographed by the light microscope and Image-Pro Plus 6.0. The results show that zebra adrenal capsule is covered with thick connective tissue, which is about 230 μm. A large number of nerves and blood vessels are distributed in the capsule. The area of cortex is about 5 times larger than medullae. Zona glomerulosa is thin, about 300？m. The cells were arranged as column and ball. Zona fasciculata with the thickness of 1 750 μm is 6 times as thick as zona glomerulosa. The cells were ar- ranged in cord. Zona reticular with the thickness of 250 wm was closely adjacent to medulla and formed a jagged boundary. The medulla with the area of 4 mm2 was deeply dyed. It was concluded that some sympathetic ganglion cells were found in the medulla arranged in groups and surrounded with zona reticular cells but lots of the cells were found in zona reticular. Some connective tissue with chromaffin cells was found in the medulla center vein. The purpose of the present study provides reliable evidences for further study on morphology, physiology and pathology of the zebra.

慢性低氧大鼠肾上腺皮质球状带的变化

将Ｗｉｓｔａｒ大鼠喂养在逐渐降低的常压低氧条件下，用氮气和空气的混合气体调节氧含量。氧浓度由正常含量逐步降低为１５％、１２％、１０％、８％，最后降至７％，实验共进行１１２ｄ。结果显示低氧动物体重下降，肾上腺重量减少，肾上腺皮质球状带萎缩，脂质丢失，球状带细胞线粒体肿胀和空泡变性，溶酶体增多。表明在慢性常压低氧中，当吸入气氧含量降至７％时，可导致肾上腺皮质球状带细胞超微结构改变，从而影响醛固酮的合成与分泌。

Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart diseases.Among the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)activity.Nicotine,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in smokers.Aldosterone has various direct and indirect adverse cardiac effects.It is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 receptors.RAAS activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease development.METHODS We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and secretion.RESULTS In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R cells.Importantly,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 expression.CONCLUSION Adrenalβarrestin1 upregulation is one of the mechanisms by which tobacco compounds,like nicotine,promote cardio-toxic hyperaldosteronism in vitro and in vivo.Thus,adrenalβarrestin1 represents a novel therapeutic target for tobaccorelated heart disease prevention or mitigation.

苯二氮受体调控醛固酮分泌机制中Ca^(2+)和cAMP的作用

外周型苯二氮受体的配体PK11195增强大鼠肾上腺皮质球状带细胞醛固酮分泌的效应可被主要作用于胞浆膜Ca^(2+)通道的阻断剂硝苯啶所取消,而不被选择性作用于线粒体Ca^(2+)通道的阻断剂硝苯啶呋海因(Da—ntrolene)所取消。PK11195在其增强醛固酮分泌的最大效应条件下并不影响球状带细胞内cAMP水平。本文的结果表明苯二氮(?)受体调控醛固酮分泌的机制中,细胞内信使物质不是cAMP,也不是来自线粒体的Ca^(2+),而是来自胞浆膜外的Ca^(2+)。

The Role of Ca^(2+) and Cyclic AMP in the Modulation of BenzodiazepineReceptor on Aldosterone Secretion

PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium channel in plasma membrane, but could not be abolished bydantrolene, a selective blocker of mitochondria calcium channel. Even under the condition of themaximum stimulative effects on aldosterone secretion, PK11195 could not change the cyclic AMP（cAMP） content in isolated glomerulosa cells. These results indicated that in the modulatory mecha-nism of benzodiazepine receptor on aldosterone secretion, the intracellular messenger might be theCa2+ from extracellular Ca2+ pool, but not the Ca2+ from mitochondria Ca2+ pool or cAMP.