The role of the cAMP/PKA signalling pathway in the inhibitory influence of melatonin on oxytocin and vasopressin secretion from the rat hypothalamo-neurohypophysial system
The role of the cAMP/PKA signalling pathway in the inhibitory influence of melatonin on oxytocin and vasopressin secretion from the rat hypothalamo-neurohypophysial system
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DOI：
10.5603/ep.a2018.0051
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发表时间：
2018-09-01
影响因子：
2.1
通讯作者：
Roszczyk, Magdalena
中科院分区：
文献类型：
--
作者：
Juszczak, Marlena;Krzyminska, Anna;Roszczyk, Magdalena
引言：褪黑激素被发现在体外抑制毛喉素刺激的催产素（OT）和加压素（VP）的释放。本研究的目的是评估环3 '，5'-腺苷酸/蛋白激酶A在细胞凋亡中的作用。体外大鼠下丘脑-神经垂体（H-NH）系统的OT和VP分泌的褪黑激素依赖性抑制中的cAMP/PKA信号传导途径。将H-NH外植体置于1 ml正常Krebs-Ringer（nK-R）缓冲液中，并首先在对照缓冲液中或在PKA抑制剂（即cAMPS-Rp或H-89）存在下预孵育30分钟。接着，将它们在nK-R缓冲液中孵育{流体F1}，然后在富含褪黑激素（10（-9）M或10（-7）M）和/或PKA激活剂（即cAMP类似物（8-Br-cAMP））或它们的载体的缓冲液F1中孵育{流体F2}。结果：8-Br-cAMP能促进H-NH外植体分泌OT和VP，而PKA抑制剂则能消除8-Br-cAMP对OT和VP分泌的刺激作用。在对照条件下，褪黑激素（10（-7）M）减少了H-NH系统的基础OT和VP输出，并抑制（在研究的两种浓度下）cAMP类似物刺激的两种神经激素的释放。褪黑激素对OT和VP释放的影响被完全阻断时，cAMPS-RP，而不是H-89，被用来破坏cAMP/ /PKA pathway.Conclusions：褪黑激素采用cAMP/PKA信号通路抑制OT和VP分泌大鼠H-NH系统，尽管如此，其他cAMP介导的机制不排除。
Introduction: Melatonin was found to inhibit forskolin-stimulated oxytocin (OT) and vasopressin (VP) release in vitro. The purpose of the present investigation was to evaluate the contribution of the cyclic 3',5'-adenosine monophosphate/protein kinase A (cAMP/PKA) signalling pathway in melatonin-dependent inhibition of OT and VP secretion from the rat hypothalamo-neurohypophysial (H-NH) system in vitro.Material and methods: The H-NH explants were placed in 1 ml of normal Krebs-Ringer (nK-R) buffer and first preincubated for 30 min in control buffer or in the presence of PKA inhibitor, i.e. cAMPS-Rp or H-89. Next, they were incubated in nK-R buffer {fluid F1} and then in buffer as Fl enriched with melatonin (10(-9) M or 10(-7) M) and/or PKA activator, i.e. cAMP analogue (8-Br-cAMP), or their vehicles {fluid F2}. After 20 min of incubation in fluid Fl and then F2, the media were collected and frozen, to be assayed for OT and VP by the RIA.Results: 8-Br-cAMP increased OT and VP secretion when the H-NH explants were preincubated in control medium, while PKA inhibitors eliminated its stimulatory effect on OT and VP release. Melatonin (10(-7) M) diminished basal OT and VP output from the H-NH system, and inhibited (at both concentrations studied) the cAMP analogue-stimulated release of both neurohormones under control conditions. The effect of melatonin on OT and VP release was completely blocked when cAMPS-Rp, but not H-89, was used to disrupt the cAMP/ /PKA pathway.Conclusions: Melatonin employs the cAMP/PKA signalling pathway to inhibit OT and VP secretion from the rat H-NH system; nonetheless, other cAMP-mediated mechanisms are not excluded.