NPY, ET-1, and Ang II nuclear receptors in human endocardial endothelial cellsThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell.

Abstract

Neuropeptide Y (NPY), endothelin-1 (ET-1), and angiotensin II (Ang II) are peptides that are known to play many important roles in cardiovascular homeostasis. The physiological actions of these peptides are thought to be primarily mediated by plasma membrane receptors that belong to the G-protein-coupled receptor superfamily. However, there is increasing evidence that suggests the existence of functional G-protein-coupled receptors at the level of the nucleus and that the nucleus could be a cell within a cell. Here, we review our work showing the presence in the nucleus of the NPY Y(1) receptor, the ET(A) and ET(B) receptors, as well as the AT(1) and AT(2) receptors and their respective ligands. This work was carried out in 20-week-old fetal human endocardial endothelial cells. Our results demonstrate that nuclear Y1, AT(1), and ET(A) receptors modulate nuclear calcium in these cells.

Neuropeptide Y (NPY) and NPY receptors in the cardiovascular system: implication in the regulation of intracellular calciumThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

“…Our recent work in human EECs highly suggested the presence of NPY at the cytosolic and nuclear levels (Jacques et al 2003a(Jacques et al , 2006a(Jacques et al , 2006b. As can be seen in Fig.…”

“…In accordance with this nuclear localization of NPY and its Y 1 receptor, there is plenty of evidence in the literature demonstrating the presence, not only of G-protein-coupled receptors (GPCRs), but also of channels, exchangers, enzymes, pumps, and hormones at the level of the nucleus (for a detailed review refer to Bkaily et al 2003Bkaily et al , 2006. Such nuclear presence of the Y 1 receptor provides a new mechanism of Y 1 receptor nuclear signaling (for more details please refer to Jacques et al 2006b andBkaily et al 2006). Thus, NPY would be able to specifically activate its nuclear membranes' receptor, rather than having only an indirect effect on the nucleus via activation of receptors localized at the plasma membrane (Jacques et al 2006b).…”

“…Such nuclear presence of the Y 1 receptor provides a new mechanism of Y 1 receptor nuclear signaling (for more details please refer to Jacques et al 2006b andBkaily et al 2006). Thus, NPY would be able to specifically activate its nuclear membranes' receptor, rather than having only an indirect effect on the nucleus via activation of receptors localized at the plasma membrane (Jacques et al 2006b). In addition, this suggests that an increase in nucleoplasmic Ca 2+ levels may lead to the release of NPY from the nucleoplasm into the perinucleoplasm by Ca 2+ -dependent exocytosis (Bkaily et al 2003;Rettig and Neher 2002;Jacques et al 2006b) to activate its inner nuclear envelope membrane receptors (Bkaily et al 2003;Jacques et al 2006b).…”

“…Thus, NPY would be able to specifically activate its nuclear membranes' receptor, rather than having only an indirect effect on the nucleus via activation of receptors localized at the plasma membrane (Jacques et al 2006b). In addition, this suggests that an increase in nucleoplasmic Ca 2+ levels may lead to the release of NPY from the nucleoplasm into the perinucleoplasm by Ca 2+ -dependent exocytosis (Bkaily et al 2003;Rettig and Neher 2002;Jacques et al 2006b) to activate its inner nuclear envelope membrane receptors (Bkaily et al 2003;Jacques et al 2006b). Similarly, an increase in perinucleoplasmic Ca 2+ levels may promote the release of NPY from the nuclear envelope space into the cytosol to activate its outer nuclear envelope membrane receptors (Bkaily et al 2003).…”

“…In A, B, C, and D, the color scale represents the level of fluorescence intensity of the NPY and the Y1 receptor antisera from 0 to 255. In panels B and D, the white scale bar represents 10 and 2 mm, respectively (Modified from Jacques et al 2006b. )…”