Hultgårdh-Nilsson A, Larsson S H, Jin P, Sejersen T, Ringertz N R
Department of Medical Cell Genetics, Medical Nobel Institute, Stockholm, Sweden.
Eur J Biochem. 1990 Dec 12;194(2):527-32. doi: 10.1111/j.1432-1033.1990.tb15648.x.
Neurokinin A, a member of the tachykinin family of neuropeptides, has been identified as a mitogen for cultured smooth muscle cells. Tachykinin-induced DNA synthesis has previously been shown to be mediated by a receptor-specific mechanism and to correlate with accumulation of phosphatidylinositol 4,5-bisphosphate breakdown products. In the present experiments, we have studied intracellular pH and expression of the proto-oncogenes c-myc, c-jun and c-fos in smooth muscle cells exposed to mitogenic concentrations of neurokinin A. Growth-arrested smooth muscle cells stimulated with neurokinin A responded with an amiloride-sensitive intracellular alkalinization, indicating Na+/H+ antiport activation. c-myc and c-jun mRNA expression was only slightly elevated by neurokinin A, while c-fos expression underwent a more pronounced increase. Maximal levels of c-fos transcripts were found after 15 min and 30 min following neurokinin A stimulation. The results demonstrate that neuropeptides may influence proto-oncogene expression in smooth muscle cells and suggest a mechanism by which peripheral neurons may modulate differentiation and growth of these cells.
神经激肽A是速激肽家族神经肽的一员，已被确定为培养的平滑肌细胞的促有丝分裂原。先前已表明，速激肽诱导的DNA合成是由受体特异性机制介导的，并且与磷脂酰肌醇4,5 -二磷酸分解产物的积累相关。在本实验中，我们研究了暴露于促有丝分裂浓度神经激肽A的平滑肌细胞中的细胞内pH值以及原癌基因c-myc、c-jun和c-fos的表达。用神经激肽A刺激生长停滞的平滑肌细胞会引起对氨氯地平敏感的细胞内碱化，表明Na+/H+反向转运体被激活。神经激肽A仅使c-myc和c-jun mRNA表达略有升高，而c-fos表达则有更明显的增加。在神经激肽A刺激后15分钟和30分钟发现c-fos转录本达到最高水平。结果表明神经肽可能影响平滑肌细胞中原癌基因的表达，并提示一种外周神经元可能调节这些细胞分化和生长的机制。
