title: 1α,25-dihydroxyvitamin D(3) mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats.
abstract: The involvement of calcium-mediated signaling pathways in the mechanism of action of 1α,25-dihydroxyvitamin D(3) (1,25D) is currently demonstrated. In this study we found that 1,25D induces nongenomic effects mediated by membrane vitamin D receptor (VDRm) by modulating intermediate filament (IF) phosphorylation and calcium uptake through L-type voltage-dependent calcium channels (L-VDCC) in cerebral cortex of 10 day-old rats. Results showed that the mechanism of action of 1,25D involves intra- and extracellular calcium levels, as well as the modulation of chloride and potassium channels. The effects of L-VDCCs on membrane voltage occur over a broad potential range and could involve depolarizing or hyperpolarizing coupling modes, supporting a cross-talk among Ca(2+) uptake and potassium and chloride channels. Also, the Na(+)/K(+)-ATPase inactivation by ouabain mimicked the 1,25D action on (45)Ca(2+) uptake. The Na(+)/K(+)-ATPase inhibition observed herein might lead to intracellular Na(+) accumulation with subsequent L-VDCC opening and consequently increased (45)Ca(2+) (calcium, isotope of mass 45) uptake. Moreover, the 1,25D effect is dependent on the activation of the following protein kinases: cAMP-dependent protein kinase (PKA), Ca(2+)/calmodulin-dependent protein kinase (PKCaMII), phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase p38 (p38(MAPK)). The modulation of calcium entry into neural cells by the 1,25D we are highlighting, might take a role in the regulation of a plethora of intracellular processes. Considering that vitamin D deficiency can lead to brain illness, 1,25D may be a possible candidate to be used, at least as an adjuvant, in the pharmacological therapy of neuropathological conditions.
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors: Leila
authors: L
authors: Zanatta
authors: Paola Bez
authors: PB
authors: Goulart
authors: Renata
authors: R
authors: Gonçalves
authors: Paula
authors: P
authors: Pierozan
authors: Elisa C
authors: EC
authors: Winkelmann-Duarte
authors: Viviane Mara
authors: VM
authors: Woehl
authors: Regina
authors: R
authors: Pessoa-Pureur
authors: Fátima Regina Mena Barreto
authors: FR
authors: Silva
authors: Ariane
authors: A
authors: Zamoner
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D034961:Antigens, Nuclear; D002118:Calcium; D020746:Calcium Channels, L-Type; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018118:Chloride Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D015221:Potassium Channels; D011493:Protein Kinase C; D018167:Receptors, Calcitriol; D000254:Sodium-Potassium-Exchanging ATPase; D014807:Vitamin D; C546339:Rbfox3 protein, rat; C118756:dihydroxy-vitamin D3