Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells.
Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells.
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DOI：
10.1016/0006-291x(91)91758-5
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发表时间：
1991-09
影响因子：
3.1
通讯作者：
P. Cahill;P. Cahill;A. Hassid;A. Hassid
中科院分区：
文献类型：
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作者：
P. Cahill;P. Cahill;A. Hassid;A. Hassid
本研究旨在探讨C受体结合型心钠素类似物对血清诱导的大鼠主动脉平滑肌细胞有丝分裂的影响。为此，使用了rANF 99 - 126和一系列截短的（rANF 103 -125，rANF 103 -125）、环缺失的（des[Gln 116，Ser 117，Gly 118，Leu 119，Gly 120] rANF 102 -121-NH 2（c-ANF）和线性des（Cys 105，Cys 121）rANF 104 - 126肽类似物。已报道后两种肽对ANF-C受体具有选择性。在第3 - 19代传代培养的细胞中，rANF 99 -126、rANF 103 -126和rANF 103 - 125浓度依赖性（0.1-1000 nM）抑制血清诱导的（3 H）胸苷掺入，在1 μM时观察到每种肽的最大抑制作用（分别为40%、31%和56%）。此外，des[Cys 105，Cys 121] rANF 104 - 126浓度依赖性地抑制血清诱导的3 H胸苷掺入，而不改变基础或升高的细胞cAMP或cGMP水平。此外，胸苷掺入的减少与血清诱导的克隆细胞增殖的抑制有关。相比之下，c-ANF未能抑制血清诱导的有丝分裂，但在100 nM的浓度下，它拮抗des[Cys 105，Cys 121] rANF 104 - 126或rANF 99 - 126的抗有丝分裂作用，而对基础或升高的细胞环核苷酸水平没有任何影响。我们的结论是心房肽的抗有丝分裂作用是通过与ANF-C受体的相互作用介导的，可能是独立的细胞环核苷酸水平的变化。
The current studies were designed to explore the effects of C-receptor-binding atrial natriuretic peptide analogues on serum-induced mitogenesis in cultured rat aortic smooth muscle cells. To this end, rANF99–126and a series of truncated (rANF103–125, rANF103–125), ring-deleted (des[Gln116, Ser117, Gly118, Leu119, Gly120]rANF102–121-NH2(c-ANF) and linear des(Cys105, Cys121)rANF104–126peptide analogues were used. The latter two peptides have been reported to be selective for the ANF-C receptor. In cells subcultured between passage 3 to 19, rANF99–126, rANF103–126, and rANF103–125concentration-dependently (0.1–1000 nM) inhibited serum-induced (3H) thymidine incorporation with maximal inhibition observed at 1 μM for each peptide (∼40, 31 and 56%) respectively. Furthermore, des[Cys105, Cys121]rANF104–126inhibited serum-induced (3Hthymidine incorporation concentration-dependently without altering basal or elevated cellular cAMP or cGMP levels. Moreover, the reduction in thymidine incorporation was associated with inhibition of serum-induced clonal cell proliferation. In contrast, c-ANF failed to inhibit serum-induced mitogenesis, yet at a concentration of 100 nM it antagonized the antimitogenic effects of des[Cys105, Cys121]rANF104–126or rANF99–126without having any effect on basal or elevated cellular cyclic nucleotide levels. We conclude that the antimitogenic effect of atrial peptides is mediated through interaction with the ANF-C receptor and may be independent of changes in cellular cyclic nucleotide levels.