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Modulation of α-Adrenergic Receptors and their Intracellular Coupling in the Ischemic Heart

  • Peter B. Corr
  • K. A. Yamada
  • S. D. DaTorre
Conference paper

Summary

The α1-adrenergic receptor exists as at least two distinct subtypes, α1a and α1b. Based on hydrophobic exclusion studies and limited proteolysis of the cloned receptor, it appears to possess characteristics analogous to other membrane-bound receptors including seven membrane spanning domains, three extracellular, and three intracellular loops, with extensive glycosylation near the extracellular amino terminus. Although the receptor is coupled to phospholipase C in cardiac myocytes, with activation resulting in the production of inositol trisphosphate (IP3) and diacylglycerol, recent findings suggest that the receptor may also be linked to phospholipase A2, phospholipase D, and cyclic nucleotide Phosphodiesterase. The α1-adrenergic receptor has been shown to increase in response to myocardial ischemia in a number of different species and to mediate not only positive inotropic effects, but also to contribute substantially to arrhythmogenesis. The increase in α1-adrenergic receptors can also occur in isolated adult ventricular myocytes in response to hypoxia, a mechanism which appears to be secondary to the sarcolemmal accumulation of long-chain acylcarnitines. This increase in α1-adrenergic receptors in hypoxic myocytes is also linked to an enhanced increase in IP3 in response to receptor stimulation. These and other findings obtained in vivo during ischemia suggest that α1-adrenergic mechanisms can become prominent in myocardium under pathophysiologic conditions in which a depressed contractile state exists and may therefore serve as a secondary inotropic system. However, the arrhythmogenic effects of stimulation of the α1-adrenergic receptor in the ischemic heart in man may contribute substantially to arrhythmogenesis and, thereby, to the incidence of sudden cardiac death.

Keywords

Adrenergic Receptor Adrenergic Stimulation Inositol Trisphosphate Palmitoyl Carnitine Stimulate Protein Kinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Peter B. Corr
    • 1
    • 2
  • K. A. Yamada
    • 1
  • S. D. DaTorre
    • 1
  1. 1.Cardiovascular Division, Department of Internal Medicine and Department of PharmacologyWashington University School of MedicineSt. LouisUSA
  2. 2.Cardiovascular DivisionWashington University School of MedicineSt. LouisUSA

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