NATRIURETIC PEPTIDES INHIBIT DNA-SYNTHESIS IN CARDIAC FIBROBLASTS
NATRIURETIC PEPTIDES INHIBIT DNA-SYNTHESIS IN CARDIAC FIBROBLASTS
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DOI：
10.1161/01.hyp.25.2.227
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发表时间：
1995-02-01
期刊：
影响因子：
8.3
通讯作者：
GARDNER, DG
中科院分区：
文献类型：
--
作者：
CAO, L;GARDNER, DG
我们研究了利钠肽对新生大鼠心脏成纤维细胞原代培养物DNA合成的影响。使用I-125标记的心房利钠肽进行结合分析，在这些细胞中鉴定出单一类别的高亲和力结合位点（Kd =0.03+/-0.01 nmol/L）。在这些位点中，80%似乎是利钠肽C受体亚型，其余是A和B受体亚型。北方印迹分析证实这些细胞中存在空气三钠尿肽受体。心房利钠肽（10（-7）mol/L）对激动剂和牵张刺激的[H-3]胸苷掺入产生适度但一致的降低（17%至41%）。此外，脑利钠肽（10（-7）mol/L）、C型利钠肽（10（-7）mol/L）和脱[谷氨酰胺（18），丝氨酸（19），甘氨酸（20），亮氨酸（21），[Gly（22）]-ANF 4-23-NH 2（10（-7）-10（-6）mol/L）能拮抗生长因子依赖的[H-3]胸苷掺入（抑制范围为14%至28%）和细胞增殖，表明所有三种利钠肽受体亚型都参与了这些培养物中有丝分裂的调节。与磷酸二酯酶抑制剂共同处理，心房钠尿肽的抑制作用被放大。用8-溴-cGMP（10（-4）-10（-3）mol/L）或硝普钠（10（-4）-10（-3）mol/L）处理后，[H-3]胸苷掺入量也出现类似的减少。这些结果提示利钠肽在调节心肌肥大时成纤维细胞生长中具有重要的旁分泌作用。
We have examined the effects of the natriuretic peptides on DNA synthesis in primary cultures of neonatal rat cardiac fibroblasts. Binding analysis using I-125-labeled atrial natriuretic peptide identified a single class of high-affinity binding sites (K-d=0.03+/-0.01 nmol/L) in these cells. Of these sites, 80% appear to be of the natriuretic peptide C receptor subtype, with the remainder being A and B receptor subtypes. Northern blot analysis confirmed the presence of air three natriuretic peptide receptors in these cells. Atrial natriuretic peptide (10(-7) mol/L) effected a modest but consistent reduction in both agonist- and stretch-stimulated [H-3]thymidine incorporation (17% to 41%). Moreover, brain natriuretic peptide (10(-7) mol/L), C-type natriuretic peptide (10(-7) mol/L), and des-[Gln(18),Ser(19),Gly(20),Leu(21),Gly(22)]-ANF 4-23-NH2 (10(-7) to 10(-6) mol/L) air proved capable of antagonizing growth factor-dependent [H-3]thymidine incorporation (the inhibition ranged from 14% to 28%) and cell proliferation, suggesting that all three natriuretic peptide receptor subtypes are involved in the regulation of mitogenesis in these cultures. The inhibition by atrial natriuretic peptide was amplified by cotreatment with phosphodiesterase inhibitors. Similar reduction in [H-3]thymidine incorporation was seen after treatment with 8-bromo-cGMP (10(-4) to 10(-3) mol/L) or nitroprusside (10(-4) to 10(-3) mol/L). These results suggest an important paracrine role for the natriuretic peptides in regulating fibroblast growth during cardiac hypertrophy.