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多巴胺(DA)的矛盾效应:Giα3介导DA对催乳素(PRL)释放的抑制作用,同时掩盖其PRL释放活性。

Paradoxical effects of dopamine (DA): Gi alpha 3 mediates DA inhibition of PRL release while masking its PRL-releasing activity.

作者信息

Kineman R D, Gettys T W, Frawley L S

机构信息

Dept. of Cell Biology and Anatomy, Medical University of South Carolina, Charleston 29425-2204.

出版信息

Endocrinology. 1994 Aug;135(2):790-3. doi: 10.1210/endo.135.2.8033828.

DOI:10.1210/endo.135.2.8033828
PMID:8033828
Abstract

In an attempt to elucidate the mechanism(s) underlying the paradoxical (inhibitory vs. stimulatory) effects of DA on PRL release, we treated permeabilized pituitary cells with antibodies directed against the carboxyl-terminus of the alpha-subunit of the guanine nucleotide binding protein, Gi3. Immunoneutralization of Gi alpha 3 completely blocked the inhibitory effect of 1000 nM DA on PRL release, as assessed by reverse hemolytic plaque assays. In contrast, DA at a 100-fold lower concentration (10 nM) had no effect on PRL release under control conditions, but elicited a stimulatory response in the presence of anti-Gi alpha 3. Examination of the frequency distribution of plaque sizes indicated that suppression and augmentation of PRL secretion by DA was not attributable to distinct subpopulations of lactotropes. Taken together, these data suggest that all pituitary lactotropes have the potential to respond to the inhibitory and stimulatory activities of DA. However, the stimulatory action of this monoamine is normally masked by tonic activation of Gi alpha 3 which couples DA to its inhibitory pathway.

摘要

为了阐明多巴胺(DA)对催乳素(PRL)释放产生矛盾(抑制与刺激)作用的潜在机制,我们用针对鸟嘌呤核苷酸结合蛋白Gi3的α亚基羧基末端的抗体处理了通透化的垂体细胞。通过反向溶血空斑试验评估,Giα3的免疫中和完全阻断了1000 nM DA对PRL释放的抑制作用。相比之下,在对照条件下,浓度低100倍(10 nM)的DA对PRL释放没有影响,但在存在抗Giα3的情况下会引发刺激反应。对空斑大小频率分布的检查表明,DA对PRL分泌的抑制和增强并非归因于不同的促乳素细胞亚群。综上所述,这些数据表明,所有垂体促乳素细胞都有潜力对DA的抑制和刺激活性作出反应。然而,这种单胺的刺激作用通常被将DA与其抑制途径偶联的Giα3的紧张性激活所掩盖。

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引用本文的文献

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Effects of the estrous cycle stage on the prolactin secretory response to dopamine in vitro.发情周期阶段对体外催乳素分泌对多巴胺反应的影响。
Endocrine. 1996 Feb;4(1):59-63. doi: 10.1007/BF02738875.
2
Dynamic organisation of prolactin gene expression in living pituitary tissue.活垂体组织中催乳素基因表达的动态组织。
J Cell Sci. 2010 Feb 1;123(Pt 3):424-30. doi: 10.1242/jcs.060434.
3
Relationships between dopamine-induced changes in cytosolic free calcium concentration ([Ca2+]i) and rate of prolactin secretion. Elevated [Ca2+]i does not indicate prolactin release.
多巴胺诱导的胞质游离钙浓度([Ca2+]i)变化与催乳素分泌速率之间的关系。[Ca2+]i升高并不表明催乳素释放。
Endocrine. 1997 Dec;7(3):343-9. doi: 10.1007/BF02801329.
4
Dopamine D2 receptor mediates both inhibitory and stimulatory actions on prolactin release.多巴胺D2受体对催乳素的释放起着抑制和刺激的双重作用。
Endocrine. 1997 Oct;7(2):177-82. doi: 10.1007/BF02778139.