Rosmaninho-Salgado Joana, Araújo Inês M, Alvaro Ana Rita, Duarte Emília P, Cavadas Cláudia
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
J Neurochem. 2007 Nov;103(3):896-903. doi: 10.1111/j.1471-4159.2007.04899.x. Epub 2007 Sep 6.
The adrenal chromaffin cells synthesize and release catecholamine (mostly epinephrine and norepinephrine) and different peptides, such as the neuropeptide Y (NPY). NPY stimulates catecholamine release through NPY Y1 receptor in mouse chromaffin cells. The aim of our study was to determine the intracellular signaling events coupled to NPY Y1 receptor activation that lead to stimulation of catecholamine release from mouse chromaffin cells. The stimulatory effect of NPY mediated by NPY Y1 receptor activation was lost in the absence of extracellular Ca2+. On the other hand, inhibition of nitric oxide synthase and guanylyl cyclase also decreased the stimulatory effect of NPY. Moreover, catecholamine release stimulated by NPY or by the nitric oxide donor (NOC-18) was inhibited by mitogen-activated protein kinase (MAPK) and protein kinase C inhibitors. In summary, in mouse chromaffin cells, NPY evokes catecholamine release by the activation the NPY Y1 receptor, in a Ca2+-dependent manner, by activating mitogen-activated protein kinase and promoting nitric oxide production, which in turn regulates protein kinase C and guanylyl cyclase activation.
肾上腺嗜铬细胞合成并释放儿茶酚胺（主要是肾上腺素和去甲肾上腺素）以及不同的肽类，如神经肽Y（NPY）。NPY通过小鼠嗜铬细胞中的NPY Y1受体刺激儿茶酚胺释放。我们研究的目的是确定与NPY Y1受体激活相关的细胞内信号转导事件，这些事件导致小鼠嗜铬细胞儿茶酚胺释放受到刺激。在没有细胞外Ca2+的情况下，由NPY Y1受体激活介导的NPY的刺激作用丧失。另一方面，一氧化氮合酶和鸟苷酸环化酶的抑制也降低了NPY的刺激作用。此外，NPY或一氧化氮供体（NOC-18）刺激的儿茶酚胺释放受到丝裂原活化蛋白激酶（MAPK）和蛋白激酶C抑制剂的抑制。总之，在小鼠嗜铬细胞中，NPY通过激活NPY Y1受体，以Ca2+依赖的方式，通过激活丝裂原活化蛋白激酶和促进一氧化氮生成，进而调节蛋白激酶C和鸟苷酸环化酶的激活，从而引起儿茶酚胺释放。
