title: Nuclear membrane receptors for ET-1 in cardiovascular function.
abstract: Plasma membrane endothelin type A (ET(A)) receptors are internalized and recycled to the plasma membrane, whereas endothelin type B (ET(B)) receptors undergo degradation and subsequent nuclear translocation. Recent studies show that G protein-coupled receptors (GPCRs) and ion transporters are also present and functional at the nuclear membranes of many cell types. Similarly to other GPCRs, ET(A) and ET(B) are present at both the plasma and nuclear membranes of several cardiovascular cell types, including human cardiac, vascular smooth muscle, endocardial endothelial, and vascular endothelial cells. The distribution and density of ET(A)Rs in the cytosol (including the cell membrane) and the nucleus (including the nuclear membranes) differ between these cell types. However, the localization and density of ET-1 and ET(B) receptors are similar in these cell types. The extracellular ET-1-induced increase in cytosolic ([Ca](c)) and nuclear ([Ca](n)) free Ca(2+) is associated with an increase of cytosolic and nuclear reactive oxygen species. The extracellular ET-1-induced increase of [Ca](c) and [Ca](n) as well as intracellular ET-1-induced increase of [Ca](n) are cell-type dependent. The type of ET-1 receptor mediating the extracellular ET-1-induced increase of [Ca](c) and [Ca](n) depends on the cell type. However, the cytosolic ET-1-induced increase of [Ca](n) does not depend on cell type. In conclusion, nuclear membranes' ET-1 receptors may play an important role in overall ET-1 action. These nuclear membrane ET-1 receptors could be targets for a new generation of antagonists.
authors.affiliation: Dept. of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, 3001- 12 Ave. North, Sherbrooke, Quebec, Canada J1H 5N4. ghassan.bkaily@usherbrooke.ca
authors.forename: Ghassan
authors.initials: G
authors.lastname: Bkaily
authors.forename: Levon
authors.initials: L
authors.lastname: Avedanian
authors.forename: Johny
authors.initials: J
authors.lastname: Al-Khoury
authors.forename: Chantale
authors.initials: C
authors.lastname: Provost
authors.forename: Moni
authors.initials: M
authors.lastname: Nader
authors.forename: Pedro
authors.initials: P
authors.lastname: D'Orléans-Juste
authors.forename: Danielle
authors.initials: D
authors.lastname: Jacques
mesh_terms: D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D009685:Nuclear Envelope / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D017466:Receptors, Endothelin / Q000502:physiology*
chemical_list: D019332:Endothelin-1; D018160:Receptors, Cytoplasmic and Nuclear; D017466:Receptors, Endothelin