Article

Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure

Cardiology Division, VA Medical Center, San Francisco, CA, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 4.66). 11/2010; 51(4):518-28. DOI: 10.1016/j.yjmcc.2010.11.014
Source: PubMed

ABSTRACT

Evidence from cell, animal, and human studies demonstrates that α1-adrenergic receptors mediate adaptive and protective effects in the heart. These effects may be particularly important in chronic heart failure, when catecholamine levels are elevated and β-adrenergic receptors are down-regulated and dysfunctional. This review summarizes these data and proposes that selectively activating α1-adrenergic receptors in the heart might represent a novel and effective way to treat heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

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Available from: Brian Jensen, Feb 18, 2015
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    • "a 1 -AR is expressed in variety of human tissue [10] and a 1 -AR stimulation has been shown to play important roles in cellular physiological functions, such as 1) regulation of smooth muscle contraction and tone in vascular system [9], prostate, urethra, bladder [11], uterine [12] and iris [13], 2) myocardial inotropy and chronotropy [14], 3) hepatic glucose metabolism [15], 4) water secretion at salivary gland [16] and 5) neurotransmission in the central nervous system [9]. In addition, chronic a 1 -AR stimulation leads to pathophysiological responses in the various cells/tissues via both cPKC and nPKC isoform signaling pathways, including cardiac hypertrophy [17] [18], hypertension and atherosclerosis [19] [20] in cardiovascular system and portal hypertension and fibrosis in liver [21]. Despite strong interest in the mechanism underlying a 1 -AR signaling-mediated pathology, especially in cardiovascular system, little is known about the molecular mechanisms for the PKC isoform-specific kinetics of activation and translocation. "

    Full-text · Dataset · Sep 2015
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    • "α 1 -AR is expressed in variety of human tissue [10] and α 1 -AR stimulation has been shown to play important roles in cellular physiological functions, such as 1) regulation of smooth muscle contraction and tone in vascular system [9], prostate, urethra, bladder [11], uterine [12] and iris [13], 2) myocardial inotropy and chronotropy [14], 3) hepatic glucose metabolism [15], 4) water secretion at salivary gland [16] and 5) neurotransmission in central nerve system [9]. In addition, chronic α 1 -AR stimulation leads to pathophysiological responses in the various cells/ tissues via both cPKC and nPKC isoform signaling pathways, including cardiac hypertrophy [17] [18], hypertension and atherosclerosis [19] [20] in cardiovascular system and portal hypertension and fibrosis in liver [21]. Despite strong interest in the mechanism underlying α 1 -AR signaling-mediated pathology, especially in cardiovascular system, little is known about the molecular mechanisms for the PKC isoform-specific kinetics of activation and translocation. "
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    • "The role of PIP2 modulation of native cardiac KCNQ1 channels is less well established. However, in the heart, α1 adrenergic receptors (α1 AR) activate Gq signaling pathways (Jensen et al., 2011) which has been shown in heterologous expression systems to modulate IKs channels (formed by KCNQ1 and the auxiliary subunit KCNE1) in through a combination of PIP2 hydrolysis and PKC phosphorylation (Matavel and Lopes, 2009). Furthermore, KCNQ1 channel mutations associated with cardiac arrythmias in patients have been shown to affect PIP2-dependent activation, suggesting that native IKs channels are sensitive to PIP2 binding (Park et al., 2005; Li et al., 2011; Zaydman et al., 2013). "
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