Dual trophic effects of the alpha1-adrenergic receptor in cultured neonatal rat heart muscle cells

Paul Simpson, Nanette Bishopric, Shaun Coughlin, Joel Karliner, Charles Ordahl, Niel Starksen, Tanny Tsao, Neal White, Lewis Williams

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The molecular signals regulating myocardial hypertrophy are unknown. We used a new model system to study this problem. Muscle cells from the neonatal rat ventricle were cultured in serum-free medium. Control cells did not change in size over time and did not show spontaneous contractile activity. Incubation with norepinephrine or epinephrine had two major trophic effects that developed over 1-2 days. The first was stimulation of muscle cell hypertrophy or increase in size. The second was induction of spontaneous contractile activity. The hypertrophic response was mediated through an alpha1-adrenoceptor. The beating response required both alpha1- and beta1-adrenergic receptor stimulation. Alpha1 stimulation alone produced enlarged cells that did not beat. Alpha1 plus beta1 stimulation induced contractile activity even when protein synthesis and hypertrophy were inhibited. Thus, the two alpha1 responses could be dissociated, providing evidence for two independently-regulated cellular pathways for the dual alpha1 trophic effects. One pathway leads to hypertrophy. The other, which requires concomitant beta1 stimulation, controls the development of beating. Preliminary work raises the possibility that different products of inositol phospholipid hydrolysis might initiate the two alpha1 trophic pathways. Other preliminary work suggests that the growth pathway is associated with the expression of specific genes and might reflect an action of the alpha1- adrenoceptor on the cell nucleus. These studies define previously unsuspected trophic roles for the alpha1-adrenergic receptor.

Original languageEnglish (US)
Pages (from-to)45-58
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume18
Issue numberSUPPL. 5
DOIs
StatePublished - 1986

Keywords

  • alpha-adrenergic receptor, beta-adrenergic receptor, myocardial cell culture
  • gene expression
  • growth regulation
  • myocardial hypertrophy
  • oncogenes
  • phorbol esters
  • phosphoinositide turnover
  • serum-free cultures

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Simpson, P., Bishopric, N., Coughlin, S., Karliner, J., Ordahl, C., Starksen, N., Tsao, T., White, N., & Williams, L. (1986). Dual trophic effects of the alpha1-adrenergic receptor in cultured neonatal rat heart muscle cells. Journal of Molecular and Cellular Cardiology, 18(SUPPL. 5), 45-58. https://doi.org/10.1016/S0022-2828(86)80460-6