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Alpha-1 adrenergic signaling in a cardiac murine atrial myocyte (HL-1) cell line

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Abstract

Activation of alpha-1 adrenergic receptors in the heart has been shown to result in increased contractile activity, cardiac fetal gene re-expression, and myocyte hypertrophy. Three alpha-1 adrenergic receptors have been identified through molecular cloning. Due to the limited selectivities of the currently available alpha-1 adrenergic receptor antagonists, the signaling pathways activated by specific subtypes in the heart remain unresolved. To resolve this dilemma, we have used a molecular approach to identify the signaling pathways and downstream genes that are engaged in response to activation of individual alpha-1 adrenergic subtypes in cardiac cells. We have transfected constitutively active alpha-1 adrenergic receptors (α1a-S290/293-AR [1] or the α1b-S288/294-AR [2]) subtypes into the cardiac murine myocyte cell line (HL-1) and studied the signal transduction pathway(s) and cardiac gene(s) activated by them. In this study, we demonstrate that the α1a-S290/293-AR [1] subtype preferentially couples to cardiac-specific atrial natriuretic factor (ANF) gene expression, while the α1b-S288/294-AR preferentially couples to activation of mitogen-activated protein kinase (MAPK), Ets-like transcription factor-1 (Elk1) and serum response element (SRE) signaling pathways. Endogenous alpha-1 adrenergic receptors are expressed, and stimulate phosphatidylinositol-hydrolysis upon activation with the alpha-1 agonist, phenylephrine.

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Authors and Affiliations

  1. College of Osteopathic Medicine, Department of Pharmacology and Physiology, Oklahoma State University, 1111 West 17th Street, Tulsa, OK, 74107-1898, USA

    Charlene D. McWhinney

  2. Weis Center for Research, 100 North Academy Drive, Danville, Pennsylvania, 17822, USA

    Carl Hansen & Janet D. Robishaw

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  1. Charlene D. McWhinney
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  2. Carl Hansen
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  3. Janet D. Robishaw
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McWhinney, C.D., Hansen, C. & Robishaw, J.D. Alpha-1 adrenergic signaling in a cardiac murine atrial myocyte (HL-1) cell line. Mol Cell Biochem 214, 111–119 (2000). https://doi.org/10.1023/A:1007129723949

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