Brain natriuretic peptide is induced by α1-adrenergic agonists as a primary response gene in cultured rat cardiac myocytes

Deanna S. Hanford, Donna J. Thuerauf, Susan F. Murray, Christopher C. Glembotski

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

To better understand the molecular basis for increased atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) expression during overload- induced cardiac hypertrophy, we studied the induction of the genes in primary myocardial cells by the α1-adrenergic agonist, phenylephrine (PE), a potent hypertrophic agent. PE augmented the transcription of both genes to similar extents, although the time course of mRNA accumulation differed. Increases in ANF mRNA were evident only after 6-8 h of PE exposure, when transcript levels were 2-4-fold over control. However, similar increases in BNP mRNA were observed as soon as 1 h of PE exposure. Moreover, while ANF mRNA levels continued to increase through 24 h of PE treatment, maximal levels of BNP mRNA (8-10-fold over control) were observed at 4 h, after which transcript levels declined to about 3-fold over control. The early induction of the BNP mRNA by PE was independent of protein synthesis, whereas the late induction of both genes required protein synthesis. Interestingly, the early BNP induction was only partially blocked by the transcription inhibitor, actinomycin D, indicating that, in part, the inductive effects of PE might be the result of transcript stabilization. Indeed, the BNP transcript, which was shown to possess a half-life of less than 1 h in control cells, was stabilized by the addition of PE, while the ANF transcript possessed a half- life of at least 24 h under all conditions. These data indicate that the induction of BNP by α1-adrenergic agonists has characteristics of both a primary and secondary response gene, while ANF is a typical secondary response gene. Moreover, α1-adrenergic stimulation enhances BNP expression through both transcriptional activation and transcript stabilization, while ANF expression is enhanced primarily transcriptionally.

Original languageEnglish (US)
Pages (from-to)26227-26233
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number42
StatePublished - Oct 21 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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