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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Deletion of the neuropeptide Y (NPY) Y-1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion
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Deletion of the neuropeptide Y (NPY) Y-1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

机译：神经肽Y（NPY）Y-1受体基因的删除揭示了NPY对儿茶酚胺合成和分泌的调节作用

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摘要

The contribution of neuropeptide Y (NPY), deriving from adrenal medulla, to the adrenosympathetic tone is unknown. We found that in response to NPY, primary cultures of mouse adrenal chromaffin cells secreted catecholamine, and that this effect was abolished in cultures from NPY Y-1 receptor knockout mice (Y-1-/-). Compared with wild-type mice (Y-1+/+), the adrenal content and constitutive release of catecholamine were increased in chromaffin cells from Y-1-/- mice. In resting animals, catecholamine plasma concentrations were higher in Y-1-/- mice. Comparing the adrenal glands of both genotypes, no differences were observed in the area of the medulla, cortex, and X zone. The high turnover of adrenal catecholamine in Y-1-/- mice was explained by the enhancement of tyrosine hydroxylase (TH) activity, although no change in the affinity of the enzyme was observed. The molecular interaction between the Y-1 receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y-1 receptor-expressing SK-N-MC cells transfected with a TH promoter sequence. We propose that NPY controls the release and synthesis of catecholamine from the adrenal medulla and consequently contributes to the sympathoadrenal tone.
机译：肾上腺髓质衍生的神经肽Y（NPY）对肾上腺交感神经张力的贡献尚不清楚。我们发现，响应NPY，小鼠肾上腺嗜铬细胞的原代培养物分泌儿茶酚胺，并且这种作用在NPY Y-1受体敲除小鼠（Y-1-/-）的培养物中被消除。与野生型小鼠（Y-1 + / +）相比，Y-1-/-小鼠的嗜铬细胞中肾上腺素含量和儿茶酚胺的组成性释放增加。在休息的动物中，儿茶酚胺血浆浓度在Y-1-/-小鼠中较高。比较两种基因型的肾上腺，在髓质，皮质和X区的面积上均未观察到差异。尽管没有观察到该酶亲和力的变化，但酪氨酸羟化酶（TH）活性的增强解释了Y-1-/-小鼠中肾上腺儿茶酚胺的高周转率。 Y-1受体与TH之间的分子相互作用通过以下事实证明：NPY明显抑制了用TH启动子序列转染的表达Y-1受体的SK-N-MC细胞中毛喉素诱导的荧光素活性。我们建议NPY控制肾上腺髓质中儿茶酚胺的释放和合成，从而有助于交感肾上腺的语气。

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