Roles of heterotrimeric GTP-binding proteins in the progression of heart failure

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Heart failure is a major cause of death in developed countries, and the development of an epoch-making cure is desired from the viewpoint for improving the quality of life and reducing the medical cost of the patient. The importance of neurohumoral factors, such as angiotensin (Ang) II and catecholamine, for the progression of heart failure has been supported by a variety of evidence. These agonists stimulate seven transmembrane-spanning receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Using specific pharmacological tools to assess the involvement of G protein signaling pathways, we have revealed that á subunit of G q (Gα q) activates Ca 2+-dependent hypertrophic signaling through diacylglycerol-activated transient receptor potential canonical (TRPC) channels (TRPC3 and TRPC6: TRPC3/6). In contrast, activation of Gα 12 family proteins in cardiomyocytes confers pressure overload-induced cardiac fibrosis via stimulation of purinergic P2Y 6 receptors induced by extracellular nucleotides released from cardiomyocytes. In fact, direct or indirect inhibition of TRPC3/6 or P2Y 6 receptors attenuates pressure overload-induced cardiac dysfunction. These findings will provide a new insight into the molecular mechanisms underlying pathogenesis of heart failure.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalJournal of Pharmacological Sciences
Volume117
Issue number1
DOIs
Publication statusPublished - Sep 22 2011

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Heterotrimeric GTP-Binding Proteins
Heart Failure
GTP-Binding Proteins
Cardiac Myocytes
Purinergic P2Y Receptors
Transient Receptor Potential Channels
Pressure
Diglycerides
Developed Countries
Angiotensin II
Catecholamines
Cause of Death
Fibrosis
Nucleotides
Quality of Life
Pharmacology
Costs and Cost Analysis
Proteins
purinoceptor P2Y6

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Molecular Medicine

Cite this

Roles of heterotrimeric GTP-binding proteins in the progression of heart failure. / Nishida, Motohiro.

In: Journal of Pharmacological Sciences, Vol. 117, No. 1, 22.09.2011, p. 1-5.

Research output: Contribution to journalReview article

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