Johnson A, Lermioglu F, Garg U C, Morgan-Boyd R, Hassid A
Department of Pharmacology, University of Tennessee, Memphis 38163.
Biochem Biophys Res Commun. 1988 Apr 29;152(2):893-7. doi: 10.1016/s0006-291x(88)80123-2.
We have investigated the effect of atrial natriuretic hormone on serum-induced mitogenesis in cultured rat mesangial cells. Synthetic peptides, atriopeptin 28 and atriopeptin 24, dose-dependently decreased thymidine incorporation, with a half-maximal effect at approximately 1 nM and a maximal inhibition of approximately 60%. Moreover, atriopeptin 28 significantly decreased the clonal proliferation of mesangial cells. Atriopeptin 28 also decreased resting cytosolic Ca but had no effect on the increase induced by serum, relative to the lower baseline established by atriopeptin 28. Nevertheless, the overall effect of atriopeptin 28 on Ca was to attenuate the serum-induced increase, relative to the original resting level. These results therefore provide evidence for a novel biological effect of atrial natriuretic hormone and suggest that the antimitogenic effect may be mediated by atriopeptin-induced alterations of intracellular Ca dynamics. We speculate that atrial natriuretic hormone may be a modulator of mesangial cell mitogenesis in vivo.
我们研究了心房利钠肽对培养的大鼠系膜细胞中血清诱导的有丝分裂的影响。合成肽心房肽28和心房肽24剂量依赖性地降低了胸腺嘧啶核苷掺入,在约1 nM时达到半数最大效应,最大抑制率约为60%。此外,心房肽28显著降低了系膜细胞的克隆增殖。相对于心房肽28建立的较低基线,心房肽28还降低了静息胞质钙,但对血清诱导的钙增加没有影响。然而,相对于原始静息水平,心房肽28对钙的总体作用是减弱血清诱导的钙增加。因此,这些结果为心房利钠肽的一种新的生物学效应提供了证据,并表明抗有丝分裂作用可能由心房肽诱导的细胞内钙动力学改变介导。我们推测心房利钠肽可能是体内系膜细胞有丝分裂的调节剂。