COORDINATIVE MINERALOCORTICOID AND GLUCOCORTICOID RECEPTOR-MEDIATED CONTROL OF RESPONSES TO SEROTONIN IN RAT HIPPOCAMPUS
COORDINATIVE MINERALOCORTICOID AND GLUCOCORTICOID RECEPTOR-MEDIATED CONTROL OF RESPONSES TO SEROTONIN IN RAT HIPPOCAMPUS
复制标题
DOI：
10.1159/000126135
复制
发表时间：
1992-03-01
影响因子：
4.1
通讯作者：
DEKLOET, ER
中科院分区：
文献类型：
--
作者：
JOELS, M;DEKLOET, ER
在先前的研究中，我们发现选择性地占据肾上腺切除(ADX)大鼠海马片上的盐皮质激素受体(MR)可以减轻5-羟色胺(5-HT)引起的CA1区锥体神经元膜超极化和阻力降低。在本研究中，我们使用选择性MR和GR配体的组合或不同浓度的内源性混合激动剂皮质酮，在海马片上建立了既有MRS又有糖皮质激素受体(GRs)对5HT的反应。我们观察到GR激动剂RU 28362阻断MR激动剂醛固酮对3、10和30-mU-M5HT反应的减弱作用；RU 28362本身不影响5HT反应。如果在体外持续灌流低浓度的皮质酮(0.5 nM，接近MR的Kd)，5HT的反应被稳定地抑制，延迟2 h，而高浓度的皮质酮(5 nM，GR的Kd附近)仅暂时降低5HT的反应。最后，假手术大鼠(血浆皮质酮水平相对较高)脑片中的5HT反应与ADX大鼠脑片中的反应相似。这些数据表明，先前报道的MR介导的5HT反应的减弱可能仅限于肾上腺皮质活动较低的条件，或者是MR和GR介导的效应的平衡被破坏的病理生理条件。
In a previous study we showed that selective occupation of the mineralocorticoid receptor (MR) in hippocampal slices from adrenalectomized (ADX) rats attenuates the membrane hyperpolarization and resistance decrease induced in CA1 pyramidal neurons by serotonin (5HT). In the present study we established responses to 5HT in the hippocampal slice when not only MRs but also glucocorticoid receptors (GRs) were occupied, using either a combination of selective MR and GR ligands or different concentrations of the endogenous mixed agonist corticosterone. We observed that the GR agonist RU 28362 blocks the attenuating action of the MR agonist aldosterone on responses to 3, 10 and 30-mu-M 5HT; RU 28362 by itself did not affect 5HT responses. If a low concentration of the mixed agonist corticosterone (0.5 nM, close to the Kd for the MR) was continuously perfused in vitro, 5HT responses were steadily depressed with a delay of 2 h, while high levels of corticosterone (5 nM, around Kd for GR) only temporarily reduced 5HT responses. Finally, 5HT responses in slices from sham-operated rats (with relatively high plasma corticosterone levels) were similar to the responses obtained in slices from ADX rats. These data suggest that the previously reported MR-mediated attenuation of 5HT responses may be limited to conditions of low adrenocortical activity or pathophysiological conditions where the balance of MR- and GR-mediated effects is disturbed.