NDLI: Rapid accumulation of cyclic GMP near activated vitamin D receptors.

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Rapid accumulation of cyclic GMP near activated vitamin D receptors.

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Rapid accumulation of cyclic GMP near activated vitamin D receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Barsony, J. Marx, S. J.
Description	Author Affiliation: Barsony J ( Mineral Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892.);
Abstract	The mechanisms of early calcitriol (1 alpha,25-dihydroxycholecalciferol) effects, including its receptor activation process as well as its 'nongenomic' effects, are poorly understood. Calcitriol causes a rapid accumulation of cGMP, dependent on the presence of normal vitamin D receptors (VDRs). We recently developed an immunocytology method based on rapid microwave fixation suitable to detect the locations of agonist-induced intracellular cGMP accumulation. With the same technique we found that calcitriol induces stepwise and rapid reorganization of VDRs. Here we used this technique to study the subcellular compartmentalization of cGMP accumulation after exposure of cells to various steroid-related agonists and to study the spatial relationship between cGMP accumulation and VDRs. Calcitriol (10 nM) within 15 sec caused clumping of VDRs and accumulation of cGMP around VDR clumps; thereafter (up to 5 min), the cGMP accumulation surrounded VDRs throughout their stepwise reorganization. In fibroblasts from subjects with mutations affecting VDR function, we found disruptions of the calcitriol-induced patterns of cGMP accumulation analogous to the disruptions of VDR reorganization. The colocalization of cGMP accumulation with reorganizing VDRs at early moments after calcitriol addition indicates transduction of the cGMP increase by VDRs inside the cell, rather than by components in the plasma membrane. Other steroid-related agonists caused compartmentalized and sequential changes in cGMP accumulation that seemed specific for each class of agonist. Our findings suggest that compartmentalized cGMP accumulation is an early and common step during activation of steroid-related receptors.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	88
Language	English
Publisher	National Academy of Sciences
Publisher Date	1991-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Calcitriol Pharmacology Cyclic GMP Metabolism Receptors, Steroid Physiology Skin Animals Cell Line Cells, Cultured Dexamethasone Dihydrotestosterone Estradiol Fibroblasts Cytology Drug Effects Glucocorticoids Kinetics Receptors, Calcitriol Tretinoin Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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