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Receptors and ionic transporters in nuclear membranes: new targets for therapeutical pharmacological interventions

Journal

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Volume 90, Issue 8, Pages 953-965

Publisher

CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/Y2012-077

Keywords

nuclear membrane; GPCR; ET-1; Ang II; NPY

Funding

  1. Canadian Institutes of Health Research (CIHR)
  2. Natural Sciences and Engineering Research Council of Canada (NSERC)
  3. Heart and Stroke Foundation of Quebec (HSFQ)

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Work from our group and other laboratories showed that the nucleus could be considered as a cell within a cell. This is based on growing evidence of the presence and role of nuclear membrane G-protein coupled receptors and ionic transporters in the nuclear membranes of many cell types, including vascular endothelial cells, endocardial endothelial cells, vascular smooth muscle cells, cardiomyocytes, and hepatocytes. The nuclear membrane receptors were found to modulate the functioning of ionic transporters at the nuclear level, and thus contribute to regulation of nuclear ionic homeostasis. Nuclear membranes of the mentioned types of cells possess the same ionic transporters; however, the type of receptors is cell-type dependent. Regulation of cytosolic and nuclear ionic homeostasis was found to be dependent upon a tight crosstalk between receptors and ionic transporters of the plasma membranes and those of the nuclear membrane. This crosstalk seems to be the basis for excitation-contraction coupling, excitation-secretion coupling, and excitation - gene expression coupling. Further advancement in this field will certainly shed light on the role of nuclear membrane receptors and transporters in health and disease. This will in turn enable the successful design of a new class of drugs that specifically target such highly vital nuclear receptors and ionic transporters.

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