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L-芳香族氨基酸脱羧酶在盐摄入后5-羟色胺刺激醛固酮分泌中的作用。

The role of L-aromatic amino acid decarboxylase in serotonin-stimulated aldosterone secretion in response to salt intake.

作者信息

Burns N, Brett L, Olverman H J, Nagatsu T, Lee M R, Williams B C

机构信息

Department of Medicine and Pathology, Western General Hospital, Edinburgh.

出版信息

Endocr Res. 1996 Nov;22(4):577-8. doi: 10.1080/07435809609043749.

Abstract

In this study we tested a new hypothesis namely that serotonin (5-hydroxytryptamine, 5-HT) could be synthesised within the zona glomerulosa of the rat adrenal gland from exogenous 5-hydroxytryptophan (5-HTP) by the enzyme L-aromatic amino acid decarboxylase (L-AAAD). A specific monoclonal antibody against L-AAAD showed that the enzyme was present predominantly in the adrenal medulla but also in the zona glomerulosa and zona fasciculata. Wistar rats, maintained on a normal (NS), low (LS) or high (HS) salt diet for one week, were sacrificed by decapitation, blood samples taken and the adrenal glands removed. Plasma aldosterone concentrations were significantly higher in the LS diet group (2.91 +/- 0.35 nM) and significantly lower in the HS diet group (0.261 +/- 0.55 nM) compared with the NS diet group (1.025 +/- 0.133 nM) (p < 0.001). Capsules from the LS diet group synthesised significantly higher maximal levels of 5-HT (2615.463 +/- 480.88 nM/mg protein) than capsules from the NS (1219.117 +/- 150.259 nM/mg protein) and the HS (968.477 +/- 214.485 nM/mg protein) salt diet groups (p < 0.05). Maximal aldosterone secretion in adrenal capsules obtained from rats on the LS diet (73.428 +/- 4.053 nM/mg protein) was significantly higher than in those obtained from rats on the NS diet (41.658 +/- 1.87 nM/mg protein) (p < 0.05). Maximal aldosterone secretion in adrenal capsules from the HS diet group (30.624 +/- 2.114 nM/mg protein) was significantly lower than in the capsules from both the LS and NS groups (p < 0.05). Carbidopa (10(-4) M), a specific inhibitor of L-AAAD, markedly attenuated the secretion of aldosterone when adrenal capsules from all three salt diet groups were incubated with 10(-4) M 5-HTP (p < 0.05), but had no significant effect on basal aldosterone secretion. These results clearly demonstrate that L-AAAD is not only present in the medulla, but also in the zona glomerulosa and zona fasciculata of the rat adrenal gland. In addition, 5-HT can be synthesised in the zona glomerulosa/capsular region of the rat adrenal gland and both its biosynthesis and its ability to stimulate aldosterone secretion is increased by sodium depletion and attenuated by sodium loading. This raises the interesting possibility that L-AAAD could play a role in the regulation of aldosterone secretion during sodium deficiency in the rat by converting circulating 5-HTP (which is present in blood at concentrations exceeding 1 micromolar) into 5-HT within the adrenal cortex.

摘要

在本研究中,我们验证了一个新的假说,即血清素(5-羟色胺,5-HT)可在大鼠肾上腺球状带内由外源性5-羟色氨酸(5-HTP)通过L-芳香族氨基酸脱羧酶(L-AAAD)合成。一种针对L-AAAD的特异性单克隆抗体显示,该酶主要存在于肾上腺髓质,但也存在于球状带和束状带。将Wistar大鼠分别维持在正常(NS)、低(LS)或高(HS)盐饮食一周后,通过断头处死,采集血样并摘除肾上腺。与NS饮食组(1.025±0.133 nM)相比,LS饮食组的血浆醛固酮浓度显著更高(2.91±0.35 nM),而HS饮食组则显著更低(0.261±0.55 nM)(p<0.001)。LS饮食组的肾上腺胶囊合成的5-HT最大水平(2615.463±480.88 nM/mg蛋白)显著高于NS(1219.117±150.259 nM/mg蛋白)和HS(968.477±214.485 nM/mg蛋白)盐饮食组(p<0.05)。从LS饮食大鼠获得的肾上腺胶囊中的最大醛固酮分泌量(73.428±4.053 nM/mg蛋白)显著高于从NS饮食大鼠获得的(41.658±1.87 nM/mg蛋白)(p<0.05)。HS饮食组肾上腺胶囊中的最大醛固酮分泌量(30.624±2.114 nM/mg蛋白)显著低于LS组和NS组的胶囊(p<0.05)。L-AAAD的特异性抑制剂卡比多巴(10⁻⁴M)在将来自所有三个盐饮食组的肾上腺胶囊与10⁻⁴M 5-HTP一起孵育时,显著减弱了醛固酮的分泌(p<0.05),但对基础醛固酮分泌没有显著影响。这些结果清楚地表明,L-AAAD不仅存在于髓质中,也存在于大鼠肾上腺的球状带和束状带中。此外,5-HT可在大鼠肾上腺的球状带/包膜区域合成,其生物合成及其刺激醛固酮分泌的能力在钠缺乏时增加而在钠负荷时减弱。这提出了一个有趣的可能性,即L-AAAD可能通过在肾上腺皮质内将循环中的5-HTP(其在血液中的浓度超过1微摩尔)转化为5-HT,在大鼠钠缺乏期间醛固酮分泌的调节中发挥作用。

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