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  • 1995-1999  (2)
  • 24-epi-1α-hydroxyvitamin D2  (1)
  • Bone resorption  (1)
  • Gene targeting  (1)
  • 1
    ISSN: 1432-1440
    Keywords: Key words Inositol 1 ; 4 ; 5-trisphosphate receptor ; Calcium release from intracellular stores ; Gene targeting ; Ataxia ; Epileptic seizures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cytoplasmic calcium, which acts as a second messenger, is derived not only from outside the cell but also from intracellular stores. A receptor for inositol 1,4,5-trisphosphate (IP3), an intracellular second messenger, is located on these internal calcium stores and functions as a calcium releasing channel. The ”type 1” IP3 receptor (IP3R1) is concentrated predominantly in cerebellar Purkinje cells and is also widely present in other neural and peripheral tissues, but many of its physiological roles in these cells are still unclear. We have previously succeeded in obtaining mice with disruption of this IP3R1 gene, in which brain IP3-induced calcium release was almost completely abolished. They were rarely born alive, indicating that IP3R1 has some functions during embryonic development. Animals exhibited severe neurological symptoms, ataxia and epilepsy, and were shown to be deficient in the cerebellar long-term depression. They give us promising clues regarding the physiological roles of calcium release from internal stores and serve as a model for the relevant human disease states.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0827
    Keywords: Bone resorption ; Osteoclast formation ; Resorption lacunae ; 24-epi-1α-hydroxyvitamin D2 ; 24-epi-1α,25-dihydroxyvitamin D2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Bone-resorbing activities of 24-epi-1α-hydroxyvitamin D2 [24-epi-1α(OH)D2], 24-epi-1α,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2], and 1α,24S,25-trihydroxyvitamin D2 [1,24S,25(OH)3D2], which might be a metabolite of 24-epi-1,25(OH)2D2, were investigated. In an in vitro bone resorption test, the activity of 24-epi-1α(OH)D2 was similar to that of 1α-hydroxyvitamin D3 [1α(OH)D3] at 10-9 M-10-6 M. The activity of 24-epi-1,25(OH)2D2 was weaker than that of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] at 10-11 M-10-8 M. On the other hand, the activity of 1,24S,25(OH)3D2 was similar to that of 24-epi-1,25(OH)2D2 at 10-11 M-10-9 M. In the formation assay of osteoclast-like cells, the activity of 24-epi-1α(OH)D2 was weaker than that of 1α(OH)D3 at 10-7 M. The activity of 24-epi-1,25(OH)2D2 was almost similar to that of 1,25(OH)2D3 at 10-11 M-10-7 M. The activity of 1,24S,25(OH)3D2 was significantly weaker than that of 24-epi-1,25(OH)2D2 at 10-11 M-10-9 M. In the two experiments, the potencies of 24-epi-1,25(OH)2D2 were about 100 times higher than those of 24-epi-1α(OH)D2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1α(OH)D2 was almost similar to those of 1α(OH)D3 and 1,25(OH)2D3 and higher than those of 24-epi-1,25(OH)2D2 and 1,24S,25(OH)3D2. 24-epi-1α-(OH)D2 and 1α(OH)D3 were longer lasting than 24-epi-1,25(OH)2D2 and 1,25(OH)2D3 in this experiment. These results suggested that 24-epi-1α(OH)D2 as well as 1α(OH)D3 was converted into dihydroxy form in vivo.
    Type of Medium: Electronic Resource
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