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The mechanism of action of several peptides is thought to be primarily dependent on their interaction with specific cell surface channels and receptors that belong to the heptahelical transmembrane spanning G-protein-coupled receptor super family. Recent development of three dimension confocal microscopy allowed studying and localization of receptors, exchangers, pumps and channels at the transcellular level of many cell types. This technique permits better identification of receptors, peptides, exchangers, pumps and channels and study of their pharmacological characteristics in working single cells. Accumulating evidence from this and related techniques, suggests that channels, exchangers, pumps and receptors as well as hormones may also be present at the nuclear membranes, the nuclear envelope space and the nucleoplasm of many cell types including vascular smooth muscle, endothelial cells, hepatocytes and cardiomyocytes. We have recently demonstrated the presence of Ca2+ and K+ channels as well as Na+-H+ exchanger and receptors such as ET-1, Ang II, NPY and E2-EP3 receptors at the nuclear membranes levels as well as within the nuclear envelope space and the nucleoplasm. Stimulation of these receptors induced increase of nuclear Ca2+ as well as de novo protein synthesis. Thus, the nucleus seems to be a cell within a cell. This review will emphasize these findings and describe how nuclear channels, exchangers, pumps and receptors as well as hormones may affect cell function via modulation of nuclear and cytosolic Ca2+ as well as gene expression and apoptosis. The pharmacology of these receptors as well as their role in cell function will also be addressed.