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- Title
Intracellular calcium: a prerequisite for aldosterone action.
- Authors
Schäfer, C; Shahin, V; Albermann, L; Schillers, H; Hug, M J; Oberleithner, H
- Abstract
Transport of salt and water in various tissues is under control of the mineralocorticoid hormone aldosterone. As a liphophilic hormone, aldosterone diffuses through the plasma membrane and, then, binds to cytosolic mineralocorticoid receptors in the target cells. After binding to nuclear pore complexes, the activated receptor is translocated to the nucleus where transcription processes are initiated. After a lag period of about 20 minutes hormone-specific early mRNA transcripts leave the nucleus through nuclear pores. Some of the steps in this cascade can be followed by electrophysiology in Xenopus laevis oocyte nuclei. In addition to the genomic pathway, aldosterone exerts a rapid pre-genomic response that involves an increase in intracellular calcium. In this study, we tested for the potential role of Ca(2+) in the genomic response of the hormone. We measured the electrical resistance across the nuclear envelope in response to aldosterone, in presence and absence of intracellular Ca(2+). Nuclear envelope electrical resistance reflects receptor binding to the nuclear pore complexes ("early" resistance peak, 2 minutes after aldosterone), ongoing transcription ("transient" resistance drop, 5-15 minutes after aldosterone) and mRNA export ("late" resistance peak, 20 minutes after aldosterone). Pre-injection of the Ca(2+) chelator EGTA eliminated all electrical responses evoked by aldosterone. The transient resistance drop and the late resistance peak, induced by the hormone, were prevented by the transcription inhibitor actinomycin D, coinjected with aldosterone, while the early resistance peak remained unaffected. We conclude that (i). the presence of intracellular Ca(2+) is a prerequisite for the genomic action of aldosterone. (ii). Intracellular calcium plays a role early in the signaling cascade, either in agonist-receptor interaction, or receptor transport/docking to the nuclear pore complexes.
- Subjects
CALCIUM metabolism; CELL metabolism; OVUM physiology; RNA metabolism; ALDOSTERONE; ANIMAL experimentation; CELL culture; CELL membranes; CELL receptors; CELLULAR signal transduction; COMPARATIVE studies; GENES; BIOELECTRIC impedance; RESEARCH methodology; MEDICAL cooperation; OVUM; RESEARCH; VERTEBRATES; EVALUATION research; CHELATING agents; PHARMACODYNAMICS; PHYSIOLOGY
- Publication
Journal of Membrane Biology, 2003, Vol 196, Issue 2, p157
- ISSN
0022-2631
- Publication type
journal article