Synergistic interaction between opioid receptor blockade and alpha-adrenergic stimulation on luteinizing hormone-releasing hormone (LHRH) secretion in vitro.
Synergistic interaction between opioid receptor blockade and alpha-adrenergic stimulation on luteinizing hormone-releasing hormone (LHRH) secretion in vitro.
复制标题
阿片受体阻断和 α-肾上腺素能刺激对体外黄体生成素释放激素 (LHRH) 分泌的协同相互作用。
DOI：
10.1159/000125328
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发表时间：
1990
影响因子：
4.1
通讯作者：
Sladek,CD
中科院分区：
文献类型：
--
作者：
Clough,RW;Hoffman,GE;Sladek,CD
阿片受体阻滞剂，α-肾上腺素能受体刺激和伴随阿片受体阻滞剂和肾上腺素能刺激对LHRH神经分泌的影响进行了研究，在组织培养中使用灌流的视前区-下丘脑（POA-MBH）外植体。用纳洛酮（NAL）阻断阿片受体导致从完整的青春期后雌性大鼠获得的POA-MBH外植体的LHRH分泌增加（p < 0.05）。在清除NAL培养基后，将基础释放速率重置为较低的基线。POA-MBH外植体随后暴露于苯肾上腺素（PHEN），一种α-肾上腺素能激动剂，导致从成人外植体释放LHRH的轻微但统计学上不显著的增加。对PHEN的减弱反应可能是由于NAL暴露后LHRH释放的持续抑制，因为PHEN之前没有NAL导致LHRH释放的显著刺激。在三个独立的实验中，青春期后大鼠外植体的LHRH反应，同时PHEN和NAL是更大的，更长的时间比任何单独的物质的反应。这项研究表明，在阿片受体阻断的存在下，PHEN的刺激作用要深刻得多。PHEN和NAL相互增强的刺激作用的观察也表明，LHRH控制的每一类神经递质的单独机制。与青春期后大鼠外植体相似，从青春期前大鼠获得的外植体增加了LHRH释放，并在NAL洗脱后显示出持续抑制LHRH释放。从青春期前大鼠获得的外植体也显着增加LHRH释放响应PHEN。从青春期前大鼠外植体的LHRH释放是更大的同时阿片受体阻滞剂和α-肾上腺素能刺激的存在下，释放的LHRH的量相比，在响应于单个代理商，但是，在这种情况下，NAL和PHEN的效果似乎不协同作用。最后，β-内啡肽对基础LHRH释放没有明显的抑制作用;然而，在β-内啡肽洗脱后，LHRH释放短暂增加。结合PHEN和β-内啡肽诱导LHRH释放的双相反应，即有一个最初的增加，随后减少，随后进一步增加。这些数据表明阿片和肾上腺素能系统对LHRH释放的调节之间存在有趣的协同作用。这种相互作用的发展和性腺类固醇对这种相互作用的影响的详细分析仍有待阐明。
The effects of opioid receptor blockade, alpha-adrenergic receptor stimulation and concomitant opioid blockade and adrenergic stimulation on LHRH neurosecretion was examined in tissue culture using perifused preoptic area-mediobasal hypothalamic (POA-MBH) explants. Blockade of opioid receptors using naloxone (NAL) resulted in increased (p < 0.05) LHRH secretion from POA-MBH explants obtained from intact postpubertal female rats. After washout of the NAL-medium, basal release rate was reset to a lower baseline. Subsequent exposure of POA-MBH explants to phenylephrine (PHEN), an alpha-adrenergic agonist, resulted in a slight but statistically insignificant increase in LHRH release from adult explants. The attenuated response to PHEN may have been due to a sustained inhibition of LHRH release following the NAL exposure since PHEN not preceded by NAL resulted in a marked stimulation of LHRH release. In three separate experiments, the LHRH response in postpubertal rat explants to simultaneous PHEN and NAL was greater and more prolonged than the responses to either of the substances alone. This study demonstrates that the stimulatory effects of PHEN are much more profound in the presence of opioid receptor blockage. The observations of the stimulatory effects of PHEN and NAL potentiating each other also suggest that separate mechanisms of LHRH control by each class of neurotransmitter are present. Similar to the postpubertal rat explants, explants obtained from prepubertal rats increased LHRH release in response to NAL and showed a sustained inhibition of LHRH release following washout of NAL. Explants obtained from prepubertal rats also significantly increased LHRH release in response to PHEN. LHRH release from prepubertal rat explants was greater in the presence of simultaneous opioid receptor blockade and alpha-adrenergic stimulation compared to the amount of LHRH released in response to the individual agents; however, in this case, the effects of NAL and PHEN appeared not to synergise. Finally, beta-endorphin had no apparent inhibitory effect on basal LHRH release; however, following washout of the beta-endorphin, LHRH release increased transiently. Combined PHEN and beta-endorphin induced a biphasic response in LHRH release whereby there was an initial increase followed by a decrease and a subsequent further increase. These data suggest an intriguing synergistic interaction between the opioid and adrenergic systems on the regulation of LHRH release. Detailed analysis of the development of this interaction and the effects of gonadal steroids on this interaction remains to be elucidated.