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Oscillations in inositol 1,4,5‐trisphosphate and diacyglycerol induced by vitamin D 3 metabolites in confluent mouse osteoblasts
Author(s) -
Grosse Brigitte,
Bourdeau Agnès,
Lieberherr Michèle
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080906
Subject(s) - inositol , stimulation , diacylglycerol kinase , inositol phosphate , phospholipid , inositol trisphosphate , endocrinology , chemistry , neomycin , phosphatidylinositol , vitamin d and neurology , medicine , biophysics , biochemistry , receptor , biology , signal transduction , protein kinase c , membrane , antibiotics
For the last 5 years, attention has focused on the nongenomic effects of 1,25‐(OH) 2 D 3 , but considerably less is known about the mechanisms of the nonnuclear actions of 24,25‐(OH) 2 D 3 . The present study examines and compares the rapid (5–90 s) effects of 100 pM to 10 nM 24,25‐(OH) 2 D 3 , 10 pM to 1 nM 1,25‐(OH) 2 D 3 , and 1–100 nM 25‐OHD 3 on the formation of inositol phosphates and lipids in confluent mouse osteoblasts. 24,25‐(OH) 2 D 3 and 25‐OHD 3 effects were dose dependent; those of 1,25‐(OH) 2 D 3 , were dose dependent in a bell‐shaped manner. The two dihydroxylated metabolites induced a multiphasic response in inositol 1,4,5‐trisphosphate (IP 3 ) formation with three stimulation peaks; the IP 3 response to 25‐OHD 3 was monophasic. The amplitude of the IP 3 response to 24,25‐(OH) 2 D 3 was greater and its oscillation period was slower than that induced by 1,25‐(OH) 2 D 3 . The diacylglycerol (DAG) responses to secosteroids showed two stimulation peaks that appeared at different times depending on the secosteroid used. Pretreatment with neomycin totally inhibited the first DAG response; neomycin had no effect on the second peak of DAG induced by 25‐OHD 3 , whereas it partially blocked the second response of DAG to 24,25‐(OH) 2 D 3 and 1,25‐(OH) 2 D 3 . These data show for the first time that 24,25‐(OH) 2 D 3 can modulate phospholipid metabolism in confluent mouse osteoblasts as early as 5–10 s. The first pathway used by all three secosteroids is that of the hydrolysis of phosphatidylinositol 4,5‐bisphosphate via phospholipase C activation, leading to the formation of the two second messengers, IP 3 and DAG, since neomycin totally blocked the response. Thus, the action of these secosteroids on the osteoblast membrane may also implicate several steps of the phosphatidylcholine cycle, according to the metabolite tested. Finally, these data point to a direct interaction of vitamin D metabolites with specific membrane recognition moieties.