Neurokinin A induces expression of the c-fos, c-jun, and c-myc genes in rat smooth muscle cells.
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.
Hultgårdh-Nilsson
A
A
Department of Medical Cell Genetics, Medical Nobel Institute, Stockholm, Sweden.
Larsson
S H
SH
Jin
P
P
Sejersen
T
T
Ringertz
N R
NR
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology*; D015737:Nisoldipine / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011519:Proto-Oncogenes / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D013449:Sulfonamides; D014157:Transcription Factors; D015737:Nisoldipine; C017967:W 7; D000584:Amiloride; D015288:Neurokinin A; D004247:DNA