NPY regulates catecholamine secretion from human adrenal chromaffin cells
NPY regulates catecholamine secretion from human adrenal chromaffin cells
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DOI：
10.1210/jc.86.12.5956
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发表时间：
2001-12-01
影响因子：
5.8
通讯作者：
Grouzmann, E
中科院分区：
文献类型：
--
作者：
Cavadas, C;Silva, AP;Grouzmann, E
本工作的目的是探讨人肾上腺嗜铬细胞合成的NPY是否以自分泌/旁分泌的方式控制儿茶酚胺的释放。因此，在培养的人嗜铬细胞中同时测定了NPY和儿茶酚胺的结构性和调节性释放。此外，通过使用RT-PCR和特定激动剂和拮抗剂的组合，我们表征了这些细胞上NPY受体的表达以及它们的药理学。我们的研究结果如下。1)人嗜铬细胞结构性分泌NPY。2)尼古丁引起儿茶酚胺和NPY的释放迅速增加，NPY的这种释放比儿茶酚胺的释放更持久。3)RT-PCR显示嗜铬细胞表达Y1、Y2、Y4和Y5受体mRNA；这些受体是有功能的，因为不同的受体特异性激动剂可以诱导细胞内钙的增加。4)与NPY不同，YY肽不能刺激儿茶酚胺的释放。这一发现得到了以下观察的证实：没有受体特异性拮抗剂能够减少构成性儿茶酚胺的释放，而NPY免疫中和抗体显著减少了这种分泌。综上所述，这些数据表明，起源于肾上腺髓质的NPY局部增强了儿茶酚胺的分泌，可能是通过假定的Y3受体起作用的。
The aim of the present work was to find out whether NPY synthesized in human adrenal chromaffin cells controls in an autocrine/paracrine fashion the release of catecholamines by these cells. Accordingly, the constitutive and regulated release of both NPY and catecholamines was measured simultaneously in cultured human chromaffin cells. In addition, by using both RT-PCR and a combination of specific agonists and antagonists, we characterized the expression of NPY receptors on these cells as well as their pharmacology. Our results were as follows. 1) Human chromaffin cells constitutively secrete NPY. 2) Nicotine elicits a rapid increase in the release of both catecholamines and NPY, this release of NPY is more sustained than that of catecholamines. 3) RT-PCR shows expression of Y1, Y2, Y4, and Y5 receptor mRNA by chromaffin cells; these receptors are functional, as various receptor specific agonists elicit an increase in intracellular calcium. 4) Peptide YY, in contrast to NPY, is not able to stimulate the release of catecholamines. This finding was corroborated by the observation that no receptor-specific antagonists were able to reduce constitutive catecholamine release, whereas an NPY-immunoneutralizing antibody markedly attenuated the secretion. Taken together, these data suggest that NPY originating from the adrenal medulla locally enhances the secretion of catecholamines, presumably by acting via the putative y3 receptor.