title: G protein-coupled receptor signalling in the cardiac nuclear membrane: evidence and possible roles in physiological and pathophysiological function.
abstract: G protein-coupled receptors (GPCRs) play key physiological roles in numerous tissues, including the heart, and their dysfunction influences a wide range of cardiovascular diseases. Recently, the notion of nuclear localization and action of GPCRs has become more widely accepted. Nuclear-localized receptors may regulate distinct signalling pathways, suggesting that the biological responses mediated by GPCRs are not solely initiated at the cell surface but may result from the integration of extracellular and intracellular signalling pathways. Many of the observed nuclear effects are not prevented by classical inhibitors that exclusively target cell surface receptors, presumably because of their structures, lipophilic properties, or affinity for nuclear receptors. In this topical review, we discuss specifically how angiotensin-II, endothelin, β-adrenergic and opioid receptors located on the nuclear envelope activate signalling pathways, which convert intracrine stimuli into acute responses such as generation of second messengers and direct genomic effects, and thereby participate in the development of cardiovascular disorders.
authors.affiliation: Department of Medicine, Université de Montréal, Montréal, Québec, Canada H3C 3J7.
authors.forename: Artavazd
authors.initials: A
authors.lastname: Tadevosyan
authors.forename: George
authors.initials: G
authors.lastname: Vaniotis
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Allen
authors.forename: Terence E
authors.initials: TE
authors.lastname: Hébert
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000818:Animals; D006321:Heart / Q000502:physiology*; D006801:Humans; D009685:Nuclear Envelope / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled