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小鼠视上核中的去甲肾上腺素能调节仅通过一氧化氮途径来调节精氨酸加压素的表达,而不调节催产素的表达。

Noradrenergic regulation in mouse supraoptic nucleus involves a nitric oxide pathway only to regulate arginine-vasopressin expression and not oxytocin expression.

作者信息

Maolood Nasren, Grange-Messent Valérie, Raison Danièle, Hardin-Pouzet Hélène

机构信息

NSI, CNRS UMR 7101, Université Pierre et Marie Curie--Paris VI, Paris, France.

出版信息

J Neurosci Res. 2007 Oct;85(13):2991-9. doi: 10.1002/jnr.21394.

Abstract

Noradrenalin (NA) regulates the expression of arginine-vasopressin (AVP) and oxytocin (OT) by magnocellular neurons in the supraoptic nucleus (SON) of the hypothamalus. Nitric oxide (NO) may be one of the factors involved in the NA signaling pathway regulating AVP and OT expression. To test this possibility, we used an ex vivo experimental model of mouse hypothalamus slices. Increases in AVP and OT levels in the SON were detected by immunohistochemistry and immunoenzyme assays after 1 hr and 4 hr incubations with NA (10(-4) M). There was also an increase in the expression and activity of neuronal NOS and inducible NOS in the SON as assessed by immunohistochemical and histoenzymological analysis of NADPH-diaphorase, whereas endothelial NOS was undetectable. To specify the role of NO, the slices were treated with NA and L-arginine methyl ester (L-NAME, an NOS inhibitor; 3 microM). This treatment for 1 hr abolished the NA-induced increase in AVP. Treatment with sodium nitroprusside (SNP, an NO donor; 0.1 mM) increased AVP levels, confirming that NO regulates AVP expression. Addition of 1 mM EGTA during the incubation with NA reduced the AVP increase by half, indicating that both nNOS and iNOS activities are involved in the regulation. A 1-hr treatment with L-NAME did not prevent the increase in OT induced by NA; similarly, treatment with SNP had no effect. These findings show that NO is involved in the regulation of AVP expression by NA and that NA control of OT expression is independent of NO.

摘要

去甲肾上腺素(NA)调节下丘脑视上核(SON)中巨细胞神经元的精氨酸加压素(AVP)和催产素(OT)的表达。一氧化氮(NO)可能是参与NA信号通路调节AVP和OT表达的因素之一。为了验证这种可能性,我们使用了小鼠下丘脑切片的离体实验模型。在用NA(10⁻⁴ M)孵育1小时和4小时后,通过免疫组织化学和免疫酶测定法检测到SON中AVP和OT水平的升高。通过对NADPH-黄递酶的免疫组织化学和组织酶学分析评估,SON中神经元型一氧化氮合酶(nNOS)和诱导型一氧化氮合酶(iNOS)的表达和活性也有所增加,而内皮型一氧化氮合酶(eNOS)未检测到。为了明确NO的作用,将切片用NA和L-精氨酸甲酯(L-NAME,一种一氧化氮合酶抑制剂;3 μM)处理。这种处理1小时消除了NA诱导的AVP增加。用硝普钠(SNP,一种NO供体;0.1 mM)处理增加了AVP水平,证实NO调节AVP表达。在与NA孵育期间添加1 mM乙二醇双乙醚二胺四乙酸(EGTA)使AVP的增加减少了一半,表明nNOS和iNOS的活性都参与了调节。用L-NAME处理1小时并不能阻止NA诱导的OT增加;同样,用SNP处理也没有效果。这些发现表明,NO参与了NA对AVP表达的调节,并且NA对OT表达的控制独立于NO。

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