α1-adrenergic receptor subtype mRNAs are differentially regulated by α1-Adrenergic and other hypertrophic stimuli in cardiac myocytes in culture and in vivo: Repression of α1B and α1D but induction of α1C

D. Gregg Rokosh, Alexandre F.R. Stewart, Kevin C. Chang, Beth A. Bailey, Joel S. Karliner, S. Albert Camacho, Carlin S. Long, Paul C. Simpson

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140 Scopus citations

Abstract

The three cloned α-adrenergic receptor (AR) subtypes, α1B, α1C, and α1D, can all couple to the same effector, phospholipase C, and the reason(s) for conservation of multiple subtypes remain uncertain. All three α1-ARs are expressed natively in cultured neonatal rat cardiac myocytes, where chronic exposure to the agonist catecholamine norepinephrine (NE) induces hypertrophic growth and gene transcription. We show here, using RNase protection, that the α1-AR subtype mRNAs respond in distinctly different ways during prolonged NE exposure (12-72 h). α1B and α1D mRNA levels were repressed by NE, whereas α1C mRNA was induced. Changes in mRNA levels were mediated by an α1-AR, were not explained by altered mRNA stability, and were reflected in receptor proteins by [3H]prazosin binding. α1-AR-stimulated phosphoinositide hydrolysis and myocyte growth were not desensitized. Three other hypertrophic agonists in culture, endothelin-1, PGF2α, and phorbol 12-myristate 13-acetate, also induced α1c mRNA and repressed α1B mRNA. In myocytes from hearts with pressure overload hypertrophy, α1 mRNA changes were identical to those produced by NE in culture. These results provide the first example of a difference in regulation among α1-AR subtypes expressed natively in the same cell. Transcriptional induction of the α1C-AR could be a mechanism for sustained growth signaling through this receptor and is a common feature of a hypertrophic phenotype in cardiac myoeytes.

Original languageEnglish (US)
Pages (from-to)5839-5843
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number10
DOIs
StatePublished - Mar 8 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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