Alpha-1 adrenergic signaling in a cardiac murine atrial myocyte (HL-1) cell line.
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 (alpha1a-S290/293-AR [1] or the alpha1b-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 alpha1a-S290/293 -AR [1] subtype preferentially couples to cardiac-specific atrial natriuretic factor (ANF) gene expression, while the alpha1b-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.
McWhinney
C D
CD
Oklahoma State University, College of Osteopathic Medicine, Department of Pharmacology and Physiology, Tulsa, OK 74107-1898, USA.
Hansen
C
C
Robishaw
J D
JD
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D009320:Atrial Natriuretic Factor; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins